Synthesis of 2,6-Substituted 7-(Het)aryl-7-deazapurine Nucleobases (2,4-Disubstituted 5-(Het)aryl-pyrrolo[2,3- d ]pyrimidines)

SYNTHESIS

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9

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7

8

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7

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2017, 49, A–AB

special topic

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en

N. Sabat et al.

Special Topic

Synthesis

Synthesis of 2,6-Substituted 7-(Het)aryl-7-deazapurine Nucleo-

bases (2,4-Disubstituted 5-(Het)aryl-pyrrolo[2,3-d]pyrimidines)

Nazarii Sabat^a,b

Sabina Smoleń^a

Petr Nauš^a

Pavla Perlíková^a

Magdaléna Cebová^a

Lenka Poštová Slavětínská^a

Michal Hocek*^a,b

X

1. R–B(OH)₂

Pd(OAc)₂, TPPTS

Na₂CO_3,H₂O/MeCN

O

N

R

X

N

R

I

N

TMSCl, NaI

HN

N

Y

N

2. deprotection

(for X = OMe)

Y

N

H

Y

H

SEM

49 examples

yields 33–92%

in two steps

21 examples

yields 37–91%

X = OMe, SMe, NH₂, Me

Y = H, Me, NH₂

R = furyl, thienyl, benzofuryl, phenyl

^aInstitute of Organic Chemistry and Biochemistry, Academy

of Sciences of the Czech Republic, Flemingovo nam. 2,

16610 Prague 6, Czech Republic

^bDepartment of Organic Chemistry, Faculty of Science,

Charles University, Hlavova 8, 12843 Prague 2, Czech

Republic

hocek@uochb.cas.cz

Published as part of the Special Topic Modern Strategies for Heterocycles Synthesis

Received: 29.03.2017

Accepted after revision: 02.05.2017

Published online: 20.06.2017

nucleoside triphosphates, and incorporation in RNA and

DNA.⁷We also found that 7-hetaryl-7-deazapurine ribonu-

cleosides bearing other substituents at position 6 (OMe,

SMe, Me), compounds 2–4 (Figure 1), exert cytostatic activ-

ities comparable to the parent 7-deazaadenosines 1, where-

as the 6-oxo- 7 and 2-substituted derivatives 5, 6, and 8

were inactive.⁸On the other hand, the biological activity of

the parent 7-hetaryl-7-deazapurine nucleobases with the

same substitution patterns is not known yet, though it is

important for mechanistic considerations, because the nu-

cleobases could be converted into nucleotides by phos-

phoribosyl transferases of the salvage pathway. Therefore,

we set up the synthesis and profiling of several new types

of 7-(het)aryl-7-deazapurine bases (Figure 1).

DOI: 10.1055/s-0036-1588443; Art ID: ss-2017-c0206-st

Abstract A series of 7-(het)aryl-7-deazapurine nucleobases (5-[(het)aryl]-

2,4-disubstituted 7H-pyrrolo[2,3-d]pyrimidines) bearing NH₂, OMe,

SMe, or Me groups at position 6 and H, NH₂, or Me at position 2 were

prepared by the aqueous Suzuki–Miyaura cross-coupling reactions

from SEM-protected 7-iodo-7-deazapurines with (het)arylboronic acids

followed by deprotection. The 6-methoxy derivatives were further

transformed into 7-deazahypoxanthines or 7-deazaguanines by O-de-

methylation reactions. Unlike their ribonucleoside counterparts, the 7-

deazapurine nucleobases did not exert any significant cytostatic or anti-

viral effects.

Key words deazapurines, pyrrolo[2,3-d]pyrimidines, nucleobases,

Suzuki–Miyaura cross-coupling, deprotection, demethylation

At first, we intended to synthesize the target 7-hetaryl-

7-deazapurine bases through aqueous phase Suzuki–

Miyaura cross-coupling reactions⁹of the corresponding 7-

iodo-7-deazapurines with hetarylboronic acids (in analogy

to our previous works using this approach for the synthesis

of 6-arylpurines¹⁰or 6-aryl-7-deazapurine bases⁴). Howev-

er, we found that the aqueous Suzuki reactions of 9-unsub-

stituted 7-iodo-7-deazapurine bases proceeded less effi-

ciently and were accompanied by significant deiodination

of the starting heterocycles which lowered the yields and

complicated isolation of the products. Therefore, we

changed the strategy and decided to introduce a suitable

protecting group at position 9. Our previous experience

suggested that the 2-[(trimethylsilyl)ethoxy]methyl (SEM)

group¹¹would be suitable for the Suzuki reactions and be

easily removable at the end.

Pyrrolo[2,3-d]pyrimidines (7-deazapurines)¹are im-

portant carba-analogues of biogenic purine bases and pos-

sess diverse biological activities. [For clarity and as a refer-

ence to purines, the (7-deaza)purine nomenclature is used

in the discussion, but IUPAC names are given in the experi-

mental part.] Most importantly, some substituted 7-

deazapurine bases are potent inhibitors of several protein

kinases,²which results in diverse therapeutically relevant

biological effects. Therefore, many approaches have been

reported of the regioselective preparation of mono-, di-,

and triaryl-substituted 7-deazapurines^3,4The synthesis and

biological profiling of simple 6-substituted or 2,6-disubsti-

tuted 7-hetaryl-7-deazapurine bases have not been report-

ed yet.

In our laboratory, we discovered that the 7-hetaryl-7-

deazaadenosines 1a–g (see Figure 1) are potent cytostatics⁵

and/or inhibitors⁶of mycobacterial adenosine kinase. The

mechanism of their cytostatic effect involves activation as

Therefore, the first goal was the synthesis of the 9-SEM-

protected 7-iodo-7-deazapurine intermediates 9–15. They

were prepared from the corresponding 6-chloro-7-iodo-7-

B

N. Sabat et al.

Special Topic

Synthesis

Previously reported 7-deazapurine

nucleosides:

Cl

N

X

Cl

N

I

ii), iii) or

iv)

This work

(7-deazapurine

nucleobases):

i)

N

O

X

R

N

H

N

HN

N

X

R

SEM

16

20

9, X = OMe

10, X = SMe

11, X = NH₂

N

Y

N

HO

O

N

Y

Me

N

Me

H

O

I

i)

N

OH OH

SEM = [2-(trimethylsilyl)-

ethoxy]methyl

HN

Nanomolar cytostatic:

1a-g, X = NH₂, Y= H

2a-g, X = OMe, Y = H

3a-g, X = SMe, Y = H

4a-g, X = Me, Y = H

Inactive:

7a-g, Y = H

8a-g, Y = NH₂

N

H

N

SEM

Y

N

19

12

H

X = NH₂, OMe, SMe,

Me

Y = H, NH₂, Me

Cl

N

OMe

Cl

I

i)

ii)

N

5a-g, X = NH₂, Y = Me

6a-g, X = OMe, Y = NH₂

N

PivHN

H₂N

N

PivHN

N

H

SEM

21

17

13

O

S

Piv = pivaloyl ((t-BuCO)

O

S

O

R =

X

Cl

I

Cl

I

g

a

b

c

d

e

f

ii) or v)

i)

N

Figure 1 Previously reported biologically active 7-deazapurine nucleo-

sides and the 7-deazapurine nucleobases under study

N

Me

N

Me

N

Me

N

H

SEM

22

18

14, X = OMe

15; X = NH₂

deazapurine bases 16–18 (known compounds prepared

according to literature procedures^12–16) by alkylation with

2-[(trimethylsilyl)ethoxy]methyl chloride (SEM-Cl) under

basic conditions,¹¹followed by nucleophilic substitution at

position 6 with NaOMe, NaSMe, or NH₃(Scheme 1). In case

of 2-amino derivative 13, orthogonal protection of the ami-

no function by the pivaloyl group was introduced to avoid

alkylation at the amino group. All of these reactions pro-

ceeded smoothly to give the key intermediates 9–15 in

good overall yields on a multigram scale. The SEM-protect-

ed 6-methyl derivative 12 was prepared by alkylation of the

known 6-methyl-7-iodo-7-deazapurine 19.¹⁷

The 9-SEM-protected 6-substituted or 2,6-disubstituted

7-iodo-7-deazapurines 9–15 were then used in aqueous

Suzuki–Miyaura reactions with a series of (het)arylboronic

acids (Table 1). The choice of the (het)aryl substituents was

based on our previous experience with cytostatic nucleo-

sides 1–4 and involved small furyl or thienyl groups (their

corresponding nucleosides 1–4a–d were nanomolar cyto-

statics) and bulkier benzofuryl, dibenzofuryl, and phenyl

groups (their nucleosides 1–4e–g were non-cytotoxic but

some showed inhibition of adenosine kinases).

The aqueous Suzuki–Miyaura cross-couplings of all the

SEM-protected 7-iodo-7-deazapurines 9–15 with the

(het)aryl boronic acids were performed under standard re-

action conditions in the presence of Na₂CO₃(3 equiv) as a

base and Pd(OAc)₂(0.05 equiv) and water soluble triphenyl-

phosphine-3,3′,3′′-trisulfonic acid trisodium salt ligand

(TPPTS) (0.125 equiv) in a mixture of water/acetonitrile

(2:1) at 100 °C for 3 hours. The reactions proceeded gener-

ally very well and gave the desired SEM-protected 7-

(het)aryl-7-deazapurines 23–29a–g in good to excellent

Scheme 1 Preparation of starting deazapurine bases. Reagents and

conditions: i) NaH, SEM-Cl, DMF, 0 °C to r.t.; for 12: 71%; for 20: 75%; for

21: 88%; for 22: 89%; ii) MeONa, MeOH, reflux, 1–2 h, for 9: 96%; for 13:

90%; for 14: 79%; iii) MeSNa, EtOH, r.t., overnight, 81% of 10; iv) NH₃,

MeOH, 130 °C, quant. of 11; v) aq NH₃(26% w/w), dioxane, 120 °C, 16

h, 94% of 15.

yields (Table 1). The reactions worked nicely even with 2-

thienyl- and 2-furylboronic acids which are rather unstable

and prone to protodeboronation during the cross-

couplings. Exceptionally, in several cases 2-thienyl- and 2-

furyltributylstannanes were used in an alternative Stille

coupling with deazapurines 9 and 10 in order to get the

corresponding 7-thienyl- or 7-furyl derivatives 25a,c and

26a,c in slightly higher yields (compared to the Suzuki cou-

pling).

The SEM-protected 7-(het)aryl-7-deazapurine interme-

diates 23–29a–g were deprotected yielding the target free

deazapurine bases 30–36a–g (Table 2). The cleavage of the

2-(trimethylsilyl)ethoxy]methyl (SEM) group was per-

formed in two steps. In the first step, the SEM-deazapurine

derivatives were treated with trifluoroacetic acid resulting

in N-hydroxymethyl intermediates which were subse-

quently cleaved in the second step by treatment with aque-

ous ammonia (urotropine formation). Alternatively, the

SEM group was removed using tetrabutylammonium fluo-

ride (TBAF) in the presence of ethylenediamine (to trap the

liberated formaldehyde). This procedure was used in sever-

al cases where the target deazapurines were insufficiently

stable under strong acidic conditions. Deprotection reac-

tions gave the library of desired 7-(het)aryl-7-deazaade-

nines 30a–g, 6-amino-2-methyl-7-deazapurines 31a–g, 6-

methoxy-7-deazapurines 32a–g, 6-(methylsulfanyl)-7-

C

N. Sabat et al.

Special Topic

Synthesis

Table 1 Synthesis of SEM-Protected Deazapurines 23–29

X

N

I

R

R–B(OH)₂, Pd(OAc)₂, TPPTS

N

Na₂CO₃, H₂O/MeCN, 100 °C, 1–3 h

N

SEM

N

Y

N

Y

SEM

9–15

23–29a–g

R

Product (yield)

X = NH₂

Y = H

X = NH₂

Y = Me

X = OMe

Y = H

X = SMe

Y = H

X = Me

Y = H

X = OMe

Y = NH₂

X = OMe

Y = Me

furan-2-yl

23a (72%)

23b (93%)

23c (78%)

23d (92%)

23e (82%)

23f (95%)

23g (99%)

24a (78%)

24b (88%)

24c (97%)

24d (99%)

24e (90%)

24f (92%)

24g (98%)

25a (80%)^a

25b (89%)

25c (83%)^a

25d (98%)

25e (92%)

25f (94%)

25g (84%)

26a (82%)^a

26b (93%)

26c (76%)^a

26d (93%)

26e (87%)

26f (99%)

26g (94%)^b

27a (91%)

27b (99%)

27c (98%)

27d (94%)

27e (84%)

27f (79%)

27g (85%)

28a (71%)

28b (73%)

28c (73%)

28d (76%)

28e (70%)

28f (65%)

28g (68%)

29a (68%)

29b (76%)

29c (80%)

29d (88%)

29e (76%)

29f (71%)

29g (64%)

furan-3-yl

thiophen-2-yl

thiophen-3-yl

benzofuran-2-yl

dibenzofuran-4-yl

phenyl

^aReaction conditions: RSnBu₃, PdCl₂(PPh₃)₂, DMF, 100 °C, 1 h.

^bEstimated yield of crude product used directly in the next step.

deazapurines 33a–g, 6-methyl-7-deazapurines 34a–g, 2-

amino-6-methoxy- and 6-methoxy-2-methyl-7-deazapu-

rines 35a–g, 36a–g in good to excellent yields (Table 2).

In order to get the 6-oxo derivatives, we could not use

direct cross-coupling reactions (which did not proceed effi-

ciently). Therefore, we prepared the 6-oxo derivatives by

demethylation of 6-methoxy-7-deazapurines. Thus the 6-

methoxy-7-deazapurines 32a–g, 35a–g, and 36a–g were

transformed into 7-substituted 7-deazaguanines 38a–g and

7-deazahypoxanthines 37a–g, 39a–g (Table 3) which are 7-

substituted 7-deaza analogues of natural purine bases gua-

nine or hypoxanthine. The O-demethylation reaction¹⁸was

performed by treatment with iodotrimethylsilane generat-

ed in situ from TMSCl and NaI in acetonitrile furnishing the

desired products 37–39a–g in good yields (Table 3).

In 7-substituted 7-deazaadenines 30a–g, 7-deazahyp-

oxanthines 37a–g, and 7-deazaguanines 38a–g, which are

the closest analogues of natural nucleobases, we also per-

formed UV-vis and fluorescence spectroscopy characteriza-

Table 2 Synthesis of Free Deazapurine Bases 30–36^a

X

R

X

R

i) or ii)

N

SEM

N

H

Y

N

Y

N

23–29a–g

30–36a–g

R

Product (yield)

X = NH₂

Y = H

X = NH₂

Y = Me

X = OMe

Y = H

X = SMe

Y = H

X = Me

Y = H

X = OMe

Y = NH₂

X = OMe

Y = Me

furan-2-yl

30a (39%)

30b (66%)

30c (73%)

30d (96%)

30e (81%)

30f (80%)

30g (90%)

31a (59%)^b

31b (83%)

31c (91%)

31d (72%)

31e (98%)

31f (85%)

31g (80%)

32a (52%)

32b (77%)

32c (68%)

32d (85%)

32e (98%)

32f (98%)

32g (74%)

33a (71%)

33b (79%)

33c (83%)

33d (98%)

33e (83%)

33f (93%)

33g (82%)

34a (85%)^b

34b (57%)^b

34c (71%)^b

34d (44%)^b

34e (59%)^b

34f (84%)^b

34g (90%)^b

35a (69%)^b

35b (78%)^b

35c (72%)^b

35d (61%)^b

35e (56%)^b

35f (51%)^b

35g (54%)^b

36a (91%)

36b (61%)^b

36c (87%)

36d (58%)^b

36e (77%)

36f (83%)

36g (62%)^b

furan-3-yl

thiophen-2-yl

thiophen-3-yl

benzofuran-2-yl

dibenzofuran-4-yl

phenyl

^aReactions conditions: (i) 1. TFA, CH₂Cl₂, r.t., 4 h; 2. aq NH₃(25% [w/w]), r.t., 12 h; (ii) TBAF,

ethylenediamine, DMF, 45–50 °C, 2–7 d.

^bReaction conditions (ii) used instead of (i).

D

N. Sabat et al.

Special Topic

Synthesis

Table 3 Synthesis of 7-Deazahypoxanthines 37, 39 and 7-Deazagua-

nines 38

Table 4 UV Absorption Spectra and Fluorescence Properties of Select-

ed 7-(Het)aryl-7-deazapurine Bases

OMe

O

Compound λ_abs(nm) (ε, 10⁴)^a

λ_em(nm)^b

Φ_f^c

0.03

R

TMSCl, NaI

N

HN

30a

30b

30c

30d

30e

30f

287 (1.5)

402

–

MeCN, 80 °C, 4 h

N

Y

N

Y

N

H

277 (0.8)

–

37–39a–g

32, 35, 36a–g

283 (1.3)

425

415

390

393

368

424

–

0.01

0.11

0.17

0.02

0.01

–

280 (1.2)

R

Product (yield)

305 (2.0)

Y = H

Y = NH₂

Y = Me

286 (2.0)

furan-2-yl

37a (82%)

37b (37%)

37c (76%)

37d (73%)

37e (89%)

37f (63%)

37g (90%)

38a (64%)

38b (58%)

38c (65%)

38d (68%)

38e (77%)

38f (73%)

38g (62%)

39a (91%)

39b (61%)

39c (87%)

39d (58%)

39e (77%)

39f (83%)

39g (52%)

30g

37a

37b

37c

37d

37e

37f

281 (1.8)

furan-3-yl

291 (1.2)

thiophen-2-yl

thiophen-3-yl

benzofuran-2-yl

dibenzofuran-4-yl

phenyl

282 (0.6)

298 (1.3)

–

285 (1.0)

–

312 (2.5), 326 (1.9)

288 (2.3), 313 (1.0)

284 (1.1)

397

–

0.01

–

37g

38a

38b

38c

38d

38e

38f

–

tion (Table 4). They generally exerted absorption maxima at

277–326 nm and some of them showed rather weak fluo-

rescence. The only brighter fluorophores were 7-(dibenzo-

furyl)-7-deazaadenine and 7-deazaguanine 30f and 38f, re-

spectively, which might have potential for fluorescent label-

ling of nucleic acids.

304 (1.1)

–

292 (1.6)

–

310 (1.1)

380

–

0.03

–

300 (1.6)

318 (3.0), 332 (2.6)

289 (2.4)

360

430

–

0.13

0.36

–

All final free 7-substituted 7-deazapurine bases 30–

39a–g were evaluated against six cell lines derived from hu-

man solid tumors including lung (A549 cells) and colon

(HCT116 and HCT116p53–/–) carcinomas, as well as leuke-

mia cell lines (CCRF-CEM, CEM-DNR, K562, and K562-TAX)

and, for comparison, non-malignant BJ and MRC-5 fibro-

blasts (in analogy to previous work⁵). None of the com-

pounds showed any considerable cytotoxic or cytostatic ac-

tivity at concentrations up to 15 μM. This is an important

result in comparison with the corresponding ribonucleo-

sides 1–4 having the same substituents at the heterocyclic

aglycon. This indicates that the salvage pathway (which

would allow formation of the cytotoxic nucleosides from

these nucleobases) does not play a role in the metabolism

of nucleosides 1–4.

In conclusion, a library of 70 new 7-(het)aryl-7-

deazapurine bases bearing different substituents at posi-

tion 2 and 6 were synthesized through aqueous phase Su-

zuki–Miyaura cross coupling reactions of 9-SEM-protected

7-iodo-7-deazapurines with diverse (het)arylboronic acids

followed by the cleavage of SEM-protecting group and O-

demethylation. The title 7-deazapurine nucleobases did not

exert a cytostatic effect which is important for the mecha-

nism of action of the corresponding cytostatic nucleosides.

38g

293 (0.9)

^aAbsorption maxima [absorption coefficient ε (M^–1cm^–1)] measured in

EtOH.

^bEmission maximum in EtOH.

^cFluorescence quantum yield in EtOH measured using quinine sulfate in

0.5 M H₂SO₄(Φ_f= 0.55) as reference.

Since the title 7-substituted 7-deazapurines are direct ana-

logues of biogenic purine bases, they also have potential in

fragment-based screening of ligands of new proteins.

NMR spectra were recorded on 400 MHz (¹H at 400 MHz, ¹³C at 100.6

MHz) or 500 MHz (¹H at 500 MHz, ¹³C at 125.7 MHz, ¹⁹F at 470.3 MHz)

Bruker Avance spectrometers. Melting points were determined on a

Kofler block and are uncorrected. Mass spectra were measured using

electrospray ionization (ESI) on a LTQ Orbitrap XL (Thermo) for high

resolution and on a Qtof micro (Waters) for low resolution. Electron

impact (EI) mass spectra were recorded on a GCT Premier (Waters).

FT IR spectra were measured on a Nicolet Avatar 370 FT-IR using KBr

method. 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine and 2-amino-4-

chloro-7H-pyrrolo[2,3-d]pyrimidine were purchased from commer-

cial suppliers and used without any further purifications. Petroleum

ether = PE.

Compounds 11,¹²16,¹³17,¹⁴18,¹⁵19,¹⁷20,¹⁶were prepared according

to the reported procedures.

E

N. Sabat et al.

Special Topic

Synthesis

5-Iodo-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyr-

rolo[2,3-d]pyrimidine (9)

MS (ESI): m/z (%) = 509.0 (100) [M + H], 530.9 (85) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₇H₂₆N₄O₂ClISiNa: 531.0450;

Deazapurine 20 (2.5 g, 6 mmol) was suspended in dry MeOH (17 mL)

then MeONa (1.65 g, 50 mmol) was added. The mixture was refluxed

for 1 h. After cooling the mixture was poured into EtOAc and washed

with H₂O and brine. The organic layer was dried (Na₂SO₄), filtered,

and concentrated. The crude product was purified using column

chromatography (silica gel, 0–5% EtOAc/PE). Recrystallization (hex-

ane/EtOAc 2:1) afforded 9 (2.47 g, 96%) as a white solid; mp 80–82 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.11 (s, 9 H, CH₃Si), 0.80 (m, 2 H,

OCH₂CH₂Si), 3.49 (m, 2 H, OCH₂CH₂Si), 4.03 (s, 3 H, CH₃O), 5.53 (s, 2 H,

NCH₂O), 7.75 (s, 1 H, H-6), 8.45 (s, 1 H, H-2).

found: 531.0450.

2-Amino-5-iodo-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (13)

A mixture of 21 (4.585 g, 9 mmol) and MeONa (6.2 mL, 25% w/w soln,

27 mmol) in MeOH (20 mL) was stirred at 100 °C for 1 h. After cooling,

the volatiles were evaporated and the residue was partitioned be-

tween EtOAc (50 mL) and H₂O (50 mL). The organic phase was dried

(MgSO₄) and evaporated. The residue was recrystallized (hexane) to

furnish the product (3.42 g, 90%) as a white solid; mp 92–93 °C.

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.25 (CH₃Si), 17.25 (OCH₂CH₂-

Si), 51.05 (C-5), 53.91 (CH₃O), 65.90 (OCH₂CH₂Si), 72.70 (NCH₂O),

106.49 (C-4a), 132.42 (CH-6), 151.44 (CH-2), 152.04 (C-7a), 162.48

(C-4).

¹H NMR (500 MHz, DMSO-d₆): δ = –0.08 (s, 9 H, Si(CH₃)₃), 0.80 (t, J_3′,2′

= 8.1 Hz, 2 H, CH₂-3′), 3.46 (t, J_2′,3′= 8.1 Hz, 2 H, CH₂-2′), 3.93 (s, 3 H,

CH₃O-4), 5.30 (s, 2 H, CH₂-1′), 6.37 (bs, 2 H, NH₂), 7.18 (s, 1 H, CH-6).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.18 (Si(CH₃)₃), 17.32 (CH₂-3′),

51.28 (C-5), 53.24 (CH₃O-4), 65.45 (CH₂-2′), 72.15 (CH₂-1′), 98.76 (C-

4a), 127.78 (CH-6), 154.74 (C-7a), 159.85 (C-2), 163.10 (C-4).

MS (EI): m/z (%) = 405.0 (100) [M].

HRMS (EI): m/z [M] calcd for

C₁₃H₂₀N₃O₂SiI: 405.0370; found:

405.0366.

MS (ESI): m/z (%) = 421.0 (100) [M + H], 443.0 (45) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₃H₂₂N₄O₂ISi: 421.0551; found:

421.0551.

5-Iodo-4-(methylsulfanyl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (10)

MeSNa (630 mg, 8.9 mmol) was added to a suspension of 20 (1.8 g,

4.4 mmol) in abs EtOH (80 mL), and mixture was stirred at r.t. over-

night. Solvent was evaporated under reduced pressure and crude

mixture was purified by flash column chromatography (silica gel, 0–

5% EtOAc/PE). Recrystallization (hexane/EtOAc 3:1) furnished 10

(1.42 g, 81%) as a white solid; mp 94–96 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.81 (m, 2 H,

OCH₂CH₂Si), 2.63 (s, 3 H, CH₃S), 3.49 (m, 2 H, OCH₂CH₂Si), 5.55 (s, 2 H,

NCH₂O), 7.87 (s, 1 H, H-6), 8.64 (s, 1 H, H-2).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.23 (CH₃Si), 12.10 (CH₃S),

17.24 (OCH₂CH₂Si), 52.53 (C-5), 66.01 (OCH₂CH₂Si), 72.57 (NCH₂O),

116.78 (C-4a), 133.80 (CH-6), 148.73 (C-7a), 151.05 (CH-2), 161.81

(C-4).

4-Chloro-5-iodo-2-methyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (22)

Deazapurine 18 (11.74 g, 40 mmol) was added in portions to a stirred

suspension of NaH (1.76 g, 60% dispersion, 44 mmol) in dry DMF (100

mL) at 0 °C. After effervescence ceased, SEM-Cl (7.82 mL, 44 mmol)

was added at 0 °C and the mixture was stirred overnight at r.t. The

mixture was then diluted with EtOAc (250 mL) and washed with H₂O

(200 mL), and the organic phase was washed with 10% brine (4 × 100

mL) and dried (MgSO₄). Purification by column chromatography (sili-

ca gel, hexane/CH₂Cl₂1:1) provided the product (15.08 g, 89%) as a

redish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.92 (m, 2 H,

OCH₂CH₂Si), 2.73 (s, 3 H, CH₃-2), 3.52 (m, 2 H, OCH₂CH₂Si), 5.57 (s, 2 H,

NCH₂O), 7.43 (s, 1 H, H-6).

MS (EI): m/z (%) = 421.0 (100) [M].

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.49 (CH₃Si), 17.63 (OCH₂CH₂Si),

25.51 (CH₃-2), 52.30 (C-5), 66.89 (OCH₂CH₂Si), 72.90 (NCH₂O), 114.28

(C-4a), 133.54 (CH-6), 152.10 (C-7a), 152.34 (C-4), 161.49 (C-2).

HRMS (EI): m/z [M] calcd for

421.0143.

C₁₃H₂₀N₃OSiSI: 421.0141; found:

4-Chloro-5-iodo-2-pivalamido-7-{[2-(trimethylsilyl)ethoxy]meth-

MS (ESI): m/z (%) = 424.0 (100) [M + H].

yl}-7H-pyrrolo[2,3-d]pyrimidine (21)

HRMS (ESI): m/z [M + H] calcd for C₁₃H₂₀N₃OClISi: 424.0103; found:

Deazapurine 17 (5 g, 13.2 mmol) was added in portions to a stirred

suspension of NaH (0.58 g, 60% dispersion, 44 mmol) in dry DMF (50

mL) at 0 °C. After effervescence ceased, SEM-Cl (2.5 mL, 14.1 mmol)

was added at 0 °C and the mixture was stirred overnight at r.t.. The

mixture was then diluted with EtOAc (250 mL) and washed with H₂O

(200 mL), and the organic phase was washed with 10% brine (4 × 100

mL), dried (MgSO₄), and evaporated. The residue was recrystallized

(MeCN) to afford the product (5.92 g, 88%) as a pinkish solid; mp

145–146 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.1 (s, 9 H, Si(CH₃)₃), 0.87 (m, 2 H,

CH₂-3′), 1.22 (s, 9 H, CH₃-tBu), 3.52 (m, 2 H, CH₂-2′), 5.52 (s, 2 H, CH₂-

1′), 7.93 (s, 1 H, CH-6), 10.24 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.31 (Si(CH₃)₃), 17.16 (CH₂-3′),

26.98 (CH₃-tBu), 39.84 (C-2′′), 53.20 (C-5), 66.24 (CH₂-2′), 72.46 (CH₂-

1′), 112.60 (C-4a), 135.50 (CH-6), 151.30 (C-2/4), 152.15 (C-2/4),

152.44 (C-7a), 175.88 (C-1′′).

424.0104.

5-Iodo-4-methoxy-2-methyl-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (14)

A mixture of 22 (15 g, 35.4 mmol) and MeONa (16 mL, 25% w/w soln,

70 mmol) in MeOH (30 mL) was stirred at 100 °C for 2 h. After cooling

the volatiles were evaporated and the residue was partitioned be-

tween EtOAc (100 mL) and 10% brine (100 mL). The organic phase was

dried (MgSO₄) and evaporated. The residue was purified by column

chromatography (silica gel, CH₂Cl₂/hexane 1:1) to give the product

(11.74 g, 79%) as an orange oil.

IR (KBr): 3119, 2950, 2895, 1673, 1595, 1340, 1250, 1085, 918, 861,

696 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.11 (s, 9 H, CH₃Si), 0.81 (m, 2 H,

OCH₂CH₂Si), 2.54 (s, 3 H, CH₃-2), 3.48 (m, 2 H, OCH₂CH₂Si), 4.01 (s, 3 H,

CH₃O-4), 5.47 (s, 2 H, NCH₂O), 7.60 (s, 1 H, H-6).

F

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.32 (CH₃Si), 17.21 (OCH₂CH₂-

Si), 25.73 (CH₃-2), 50.88 (C-5), 53.60 (CH₃O-4), 65.76 (OCH₂CH₂Si),

72.44 (NCH₂O), 104.16 (C-4a), 131.60 (CH-6), 152.75 (C-7a), 160.53

(C-2), 162.17 (C-4).

Variations: In General Procedure A′ (GPA′), a reduced amount of cat-

alyst and ligand were used: Pd(OAc)₂(4.5 mg, 0.02 mmol, 2 mol%) and

TPPTS (28 mg, 0.05 mmol, 5 mol%) for 1 mmol of starting compound.

In General Procedure A′′ (GPA′′), boronic acid (1.1 equiv) was used. In

General Procedure A′′′ (GPA′′′), boronic acid (1.25 equiv) and TPPTS

(0.15 equiv) were used and the mixture was stirred for 1 h.

MS (ESI): m/z (%) = 420.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₄H₂₃N₃O₂ISi: 420.0599; found:

420.0600.

Stille Coupling; General Procedure B (GPB)

An argon-purged mixture of SEM-protected 7-iodo-7-deazapurine

derivative 9–10, RSnBu₃(1.2 equiv), and PdCl₂(PPh₃)₂(0.1 equiv) was

dissolved in dry DMF, heated to 100 °C and stirred for 1 h. After cool-

ing the volatiles were removed under reduced pressure and the mix-

ture was purified by flash column chromatography (silica gel, EtOAc

0–5%/PE).

4-Amino-5-iodo-2-methyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (15)

Compound 22 (4.24 g, 10.0 mmol) was dissolved in aq NH₃(26% w/w,

40 mL) and dioxane (40 mL) and heated in a steel bomb at 120 °C for

16 h. The volatiles were removed in vacuo and the residue was re-

crystallized (H₂O) to give the product (3.80 g, 94%) as a white solid.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.82 (m, 2 H,

OCH₂CH₂Si), 2.37 (s, 3 H, CH₃-2), 3.48 (m, 2 H, OCH₂CH₂Si), 5.40 (s, 2 H,

NCH₂O), 6.56 (bs, 2 H, NH₂), 7.45 (s, 1 H, H-6).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.23 (CH₃Si), 17.26 (OCH₂CH₂-

Si), 25.61 (CH₃-2), 51.61 (C-5), 65.61 (OCH₂CH₂Si), 72.07 (NCH₂O),

100.86 (C-4a), 129.25 (CH-6), 151.45 (C-7a), 157.24 (C-4), 161.02 (C-

2).

Acidic SEM Cleavage; General Procedure C (GPC)

A SEM-protected deazapurine derivative 23–29a–g (1 mmol) was dis-

solved in CH₂Cl₂(2 mL) and TFA (4 mL). After 4 h at r.t. (TLC usually

revealed full conversion of starting material), the volatiles were re-

moved by evaporation and co-evaporation with MeOH (3 ×). The resi-

due was stirred with MeOH (2 mL) and aq NH₃(25% w/w, 4 mL) for an

additional 12 h. The mixture then was evaporated to dryness and the

crude product was recrystallized or purified by flash column chroma-

tography (silica gel) prior to final crystallization.

MS (ESI): m/z (%) = 405.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₃H₂₂N₄OISi: 405.0602; found:

405.0602.

TBAF SEM Cleavage; General Procedure D (GPD)

A mixture of a SEM-protected deazapurine derivative 23–29a–g (1

mmol), TBAF (3 equiv), and ethylenediamine (6 equiv) in DMF (0.5

mL) was stirred at 50 °C for 96 h. After cooling the volatiles were re-

moved by evaporation in vacuo and co-evaporation with toluene (3

×). The residue was purified by flash column chromatography.

5-Iodo-4-methyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrro-

lo[2,3-d]pyrimidine (12)

Nucleobase 19 (1.0 g, 3.86 mmol) was added to a suspension of NaH

(201 mg, 60% dispersion, 5.02 mmol) in anhyd DMF (15 ml) under an

argon atmosphere and the mixture was stirred at r.t. for 15 min. Then

the mixture was cooled to 0 °C, SEM-Cl (717 μL, 4.05 mmol) was add-

ed and the mixture was stirred at 0 °C for a further 1.5 h. The mixture

was diluted with EtOAc and washed with brine. The organic layer was

dried (MgSO₄) and evaporated under reduced pressure. After column

chromatography (silica gel, hexane/EtOAc 10:1) protected nucleobase

12 (1.06 g, 71%) was obtained as a white amorphous solid.

Variations: In General Procedure D′ (GPD′), TBAF (4 equiv), ethylene-

diamine (8 equiv), and DMF (5.5 mL per 1 mmol of starting com-

pound) were used. The mixture was stirred at 45 °C. In General Pro-

cedure D′′ (GPD′′), TBAF (8 equiv), ethylenediamine (16 equiv), and

DMF (5.5 mL per 1 mmol of starting compound) were used. The mix-

ture was stirred at 45 °C.

¹H NMR (500 MHz, CDCl₃): δ = –0.06 (s, 9 H, CH₃Si), 0.91 (m, 2 H,

OCH₂CH₂Si), 2.99 (s, 3 H, CH₃-4), 3.51 (m, 2 H, OCH₂CH₂Si), 5.49 (s, 2 H,

NCH₂O), 7.44 (s, 1 H, H-6), 8.74 (s, 1 H, H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.48 (CH₃Si), 17.66 (OCH₂CH₂Si),

20.90 (CH₃-4), 52.74 (C-5), 66.74 (OCH₂CH₂Si), 72.64 (NCH₂O), 117.99

(C-4a), 132.76 (CH-6), 150.49 (C-7a), 151.72 (CH-2), 160.61 (C-4).

O-Demethylation Reaction; General Procedure E (GPE)

To a stirred mixture of 6-methoxy-7-deazapurine derivative 32a–g,

35a–g, 36a–g and NaI (5 equiv) in anhyd MeCN, TMSCl (5 equiv) was

added slowly and the mixture was stirred at 80 °C for 4 h. The precip-

itate was filtered off, washed carefully with MeCN, dissolved in H₂O

and the pH was adjusted to 7 using solid K₂CO₃. The product precipi-

tated and was filtered off. The product was repurified by flash col-

umn chromatography if needed.

MS (ESI): m/z (%) = 390.1 (100) [M + H], 412.1 (8) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₃H₂₁ON₃ISi: 390.04931; found:

390.04941.

4-Amino-5-(furan-2-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidine (23a)

Suzuki–Miyaura Cross-Coupling Reaction; General Procedure A

(GPA)

Compound 23a was prepared from 11 (390 mg, 1.0 mmol) and furan-

2-boronic acid (168 mg, 1.5 mmol) by GPA. Column chromatography

(0.5% MeOH/CHCl₃) gave the product (233 mg, 72%) as a yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.83 (m, 2 H,

OCH₂CH₂Si), 3.52 (m, 2 H, OCH₂CH₂Si), 5.52 (s, 2 H, NCH₂O), 6.60 (dd,

J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 6.69 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9

An argon-purged mixture of SEM-protected 7-iodo-7-deazapurine

derivative 9–15 (1 mmol), boronic acid (1.5 mmol), Na₂CO₃(318 mg, 3

mmol), Pd(OAc)₂(11 mg, 0.05 mmol), and TPPTS (71 mg, 0.125 mmol)

in H₂O/MeCN (2:1, 5 mL) was stirred at 100 °C for 3 h. After cooling,

the mixture was diluted with H₂O and extracted with CHCl₃. The or-

ganic phase was dried (MgSO₄), filtered, and evaporated and the resi-

due was purified by column chromatography (silica gel). Alternative-

ly, after cooling the mixture was directly loaded onto silica gel by co-

evaporation without aqueous work-up.

Hz, 1 H, H-3-furyl), 6.93 (bs, 2 H, NH₂), 7.75 (s, 1 H, H-6), 7.78 (dd, J_5,4

1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 8.16 (H-2).

=

G

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.21 (CH₃Si), 17.29 (OCH₂CH₂-

Si), 65.71 (OCH₂CH₂Si), 72.45 (NCH₂O), 98.91 (C-4a), 105.33 (CH-3-fu-

ryl), 106.27 (C-5), 112.13 (CH-4-furyl), 122.94 (CH-6), 142.09 (CH-5-

furyl), 148.76 (C-2-furyl), 151.26 (C-7a), 152.60 (CH-2), 157.46 (C-4).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.45 (CH₃Si), 17.72 (OCH₂CH₂Si),

66.45 (OCH₂CH₂Si), 72.79 (NCH₂O), 101.30 (C-4a), 111.93 (C-5),

122.15 (CH-2-thienyl), 122.65 (CH-6), 127.02 (CH-5-thienyl), 128.45

(CH-4-thienyl), 134.77 (C-3-thienyl), 151.20 (C-7a), 151.99 (CH-2),

156.89 (C-4).

MS (ESI): m/z (%) = 331.2 (100) [M + H], 353.2 (20) [M + Na].

MS (ESI): m/z (%) = 347.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₆H₂₃O₂N₄Si: 331.1585; found:

331.1586.

HRMS (ESI): m/z [M + H] calcd for C₁₆H₂₃ON₄SSi: 347.1356; found:

347.1356.

4-Amino-5-(furan-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidine (23b)

4-Amino-5-(benzofuran-2-yl)-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (23e)

Compound 23b was prepared from 11 (390 mg, 1.0 mmol) and furan-

3-boronic acid (168 mg, 1.5 mmol) by GPA. Column chromatography

(hexanes/EtOAc 2:1) gave the product (308 mg, 93%) as a yellowish

oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 3.57 (m, 2 H, OCH₂CH₂Si), 5.46 (bs, 2 H, NH₂), 5.58 (s, 2 H,

NCH₂O), 6.58 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.08 (s, 1 H,

H-6), 7.56 (t, J_5,2= J_5,4= 1.7 Hz, 1 H, H-5-furyl), 7.58 (dd, J_2,5= 1.6 Hz,

J_2,4= 0.9 Hz, 1 H, H-2-furyl), 8.32 (H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.71 (OCH₂CH₂Si),

66.45 (OCH₂CH₂Si), 72.75 (NCH₂O), 101.55 (C-4a), 107.13 (C-5),

111.52 (CH-4-furyl), 118.63 (C-3-furyl), 122.71 (CH-6), 139.70 (CH-2-

furyl), 144.03 (CH-5-furyl), 151.28 (C-7a), 151.89 (CH-2), 156.87 (C-

4).

Compound 23e was prepared from 11 (390 mg, 1.0 mmol) and benzo-

furan-2-boronic acid (243 mg, 1.5 mmol) by GPA. Column chromatog-

raphy (0.5% MeOH/CHCl₃) gave the product (313 mg, 82%) as a pink-

ish solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 3.59 (m, 2 H, OCH₂CH₂Si), 5.63 (s, 2 H, NCH₂O), 6.37 (bs, 2

H, NH₂), 6.88 (d, J_3,7a= 1.0 Hz, 1 H, H-3-benzofuryl), 7.28 (m, 1 H, H-5-

benzofuryl), 7.30 (m, 1 H, H-6-benzofuryl), 7.52 (m, 1 H, H-7-benzo-

furyl), 7.54 (s, 1 H, H-6), 7.58 (m, 1 H, H-4-benzofuryl), 8.35 (s, 1 H, H-

2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.45 (CH₃Si), 17.74 (OCH₂CH₂Si),

66.70 (OCH₂CH₂Si), 73.02 (NCH₂O), 99.96 (C-4a), 101.80 (CH-3-benzo-

furyl), 107.09 (C-5), 110.82 (CH-7-benzofuryl), 120.73 (CH-4-benzo-

furyl), 123.47 (CH-6), 123.60 (CH-5-benzofuryl), 124.12 (CH-6-ben-

zofuryl), 128.91 (C-3a-benzofuryl), 150.85 (C-2-benzofuryl), 151.67

(C-7a), 152.15 (CH-2), 154.25 (C-7a-benzofuryl), 156.83 (C-4).

MS (ESI): m/z (%) = 331.2 (100) [M + H], 353.1 (5) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₆H₂₃O₂N₄Si: 331.1585; found:

331.1585.

MS (ESI): m/z (%) = 381.2 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₂₀H₂₅O₂N₄Si: 381.1741; found:

381.1742.

4-Amino-5-(thiophen-2-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (23c)

Compound 23c was prepared from 11 (390 mg, 1.0 mmol) and thio-

phene-2-boronic acid (192 mg, 1.5 mmol) by GPA. Column chroma-

tography (hexanes/EtOAc 2:1) gave the product (269 mg, 78%) as a

white solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 3.58 (m, 2 H, OCH₂CH₂Si), 5.52 (bs, 2 H, NH₂), 5.59 (s, 2 H,

NCH₂O), 7.11–7.15 (m, 2 H, H-3,5-thienyl), 7.18 (s, 1 H, H-6), 7.34 (m,

1 H, H-4-thienyl), 8.33 (H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.45 (CH₃Si), 17.72 (OCH₂CH₂Si),

66.54 (OCH₂CH₂Si), 72.83 (NCH₂O), 101.25 (C-4a), 109.53 (C-5),

123.86 (CH-6), 125.65 (CH-4-thienyl), 126.38 and 127.99 (CH-3,5-

thienyl), 135.76 (C-2-thienyl), 151.22 (C-7a), 152.16 (CH-2), 156.84

(C-4).

4-Amino-5-(dibenzo[b,d]furan-4-yl)-7-{[2-(trimethylsi-

lyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (23f)

Compound 23f was prepared from 11 (390 mg, 1.0 mmol) and diben-

zo[b,d]furan-4-boronic acid (318 mg, 1.5 mmol) by GPA. Column

chromatography (0.5% MeOH/CHCl₃) gave the product (409 mg, 95%)

as a white solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.01 (s, 9 H, CH₃Si), 0.98 (m, 2 H,

OCH₂CH₂Si), 3.67 (m, 2 H, OCH₂CH₂Si), 5.31 (bs, 2 H, NH₂), 5.70 (s, 2 H,

NCH₂O), 7.39 (btd, J_8,7= J_8,9= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₂H₇O),

7.47 (t, J_2,3= J_2,1= 7.6 Hz, 1 H, H-2-C₁₂H₇O), 7.48 (ddd, J_7,6= 8.2 Hz, J_7,8

7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₂H₇O), 7.48 (s, 1 H, H-6), 7.54 (dd, J_3,2

7.5 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₂H₇O), 7.56 (dt, J_6,7= 8.2 Hz, J_6,8= J_6,9

=

0.9 Hz, 1 H, H-6-C₁₂H₇O), 7.98 (dd, J_1,2= 7.6 Hz, J_1,3= 1.3 Hz, 1 H, H-1-

MS (ESI): m/z (%) = 347.1 (100) [M + H], 369.1 (10) [M + Na].

C

₁₂H₇O), 8.01 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-

₁₂H₇O), 8.38 (s, 1 H, H-2).

HRMS (ESI): m/z [M + H] calcd for C₁₆H₂₃ON₄SSi: 347.1356; found:

347.1356.

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.40 (CH₃Si), 17.78 (OCH₂CH₂Si),

66.64 (OCH₂CH₂Si), 73.09 (NCH₂O), 101.75 (C-4a), 110.62 (C-5),

111.92 (CH-6-C₁₂H₇O), 118.82 (C-4-C₁₂H₇O), 119.90 (CH-1-C₁₂H₇O),

120.90 (CH-9-C₁₂H₇O), 123.11 (CH-8-C₁₂H₇O), 123.41 (CH-2-C₁₂H₇O),

124.14 (C-9a-C₁₂H₇O), 124.73 (CH-6), 125.05 (C-9b-C₁₂H₇O), 127.62

(CH-7-C₁₂H₇O), 127.90 (CH-3-C₁₂H₇O), 151.42 (C-7a), 151.66 (CH-2),

153.63 (C-4a-C₁₂H₇O), 156.17 (C-5a-C₁₂H₇O), 156.81 (C-4).

4-Amino-5-(thiophen-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (23d)

Compound 23d was prepared from 11 (390 mg, 1.0 mmol) and thio-

phene-3-boronic acid (192 mg, 1.5 mmol) by GPA. Column chroma-

tography (0.5% MeOH/CHCl₃) gave the product (319 mg, 92%) as a

white solid.

MS (ESI): m/z (%) = 431.2 (100) [M + H], 453.2 (10) [M + Na].

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 3.58 (m, 2 H, OCH₂CH₂Si), 5.39 (bs, 2 H, NH₂), 5.60 (s, 2 H,

NCH₂O), 7.12 (s, 1 H, H-6), 7.23 (dd, J_4,5= 4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-

thienyl), 7.32 (dd, J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.47 (dd,

J_5,4= 4.9 Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl), 8.33 (H-2).

HRMS (ESI): m/z [M + H] calcd for C₂₄H₂₇O₂N₄Si: 431.1898; found:

431.1898.

H

N. Sabat et al.

Special Topic

Synthesis

4-Amino-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyr-

rolo[2,3-d]pyrimidine (23g)

4-Amino-5-(thiophen-2-yl)-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24c)

Compound 23g was prepared from 11 (390 mg, 1.0 mmol) and phen-

ylboronic acid (183 mg, 1.5 mmol) by GPA. Column chromatography

(hexanes/EtOAc 3:1) gave the product (340 mg, 99%) as a yellowish

oil.

Compound 24c was prepared from 15 (404 mg, 1.0 mmol) and thio-

phene-2-boronic acid (192 mg, 1.5 mmol) by GPA′. Column chroma-

tography (hexanes/EtOAc 2:1) gave the product (348 mg, 97%) as a

yellowish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 3.59 (m, 2 H, OCH₂CH₂Si), 5.41 (bs, 2 H, NH₂), 5.62 (s, 2 H,

NCH₂O), 7.11 (s, 1 H, H-6), 7.39 (m, 1 H, H-p-Ph), 7.44–7.51 (m, 2 × 2

H, H-m,o-Ph), 8.43 (s, 1 H, H-2).

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 2.57 (s, 3 H, CH₃-2), 3.58 (m, 2 H, OCH₂CH₂Si), 5.38 (bs, 2

H, NH₂), 5.57 (s, 2 H, NCH₂O), 7.10 (s, 1 H, H-6), 7.10–7.13 (m, 2 H, H-

3,5-thienyl), 7.31 (m, 1 H, H-4-thienyl).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.45 (CH₃Si), 17.74 (OCH₂CH₂Si),

66.50 (OCH₂CH₂Si), 72.88 (NCH₂O), 101.05 (C-4a), 117.60 (C-5),

122.72 (CH-6), 127.46 (CH-p-Ph), 128.83 and 129.10 (CH-o,m-Ph),

134.37 (C-i-Ph), 151.24 (C-7a), 151.77 (CH-2), 156.70 (C-4).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.69 (OCH₂CH₂Si),

25.63 (CH₃-2), 66.40 (OCH₂CH₂Si), 72.53 (NCH₂O), 98.99 (C-4a),

109.35 (C-5), 123.12 (CH-6), 125.35 (CH-4-thienyl), 126.10 and

127.93 (CH-3,5-thienyl), 136.24 (C-2-thienyl), 152.33 (C-7a), 156.71

(C-4), 161.65 (C-2).

MS (ESI): m/z (%) = 341.2 (100) [M + H].

MS (ESI): m/z (%) = 361.2 (100) [M + H], 383.1 (10) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₈H₂₅ON₄Si: 341.1792; found:

341.1792.

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅ON₄SSi: 361.1513; found:

361.1514.

4-Amino-5-(furan-2-yl)-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24a)

4-Amino-5-(thiophen-3-yl)-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24d)

Compound 24a was prepared from 15 (404 mg, 1.0 mmol) and furan-

2-boronic acid (168 mg, 1.5 mmol) by GPA′. Column chromatography

(hexanes/EtOAc 2:1) gave the product (269 mg, 78%) as a yellowish

oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃-2), 3.55 (m, 2 H, OCH₂CH₂Si), 5.56 (s, 2 H,

NCH₂O), 6.11 (bs, 2 H, NH₂), 6.48 (dd, J_3,4= 3.3 Hz, J_3,5= 0.8 Hz, 1 H, H-

3-furyl), 6.51 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 7.26 (s, 1 H,

H-6), 7.49 (dd, J_5,4= 1.9 Hz, J_5,3= 0.8 Hz, 1 H, H-5-furyl).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.48 (CH₃Si), 17.67 (OCH₂CH₂Si),

25.48 (CH₃-2), 66.37 (OCH₂CH₂Si), 72.55 (NCH₂O), 97.58 (C-4a),

105.00 (CH-3-furyl), 107.29 (C-5), 111.96 (CH-4-furyl), 121.07 (CH-

6), 141.01 (CH-5-furyl), 149.31 (C-2-furyl), 152.53 (C-7a), 156.81 (C-

4), 161.57 (C-2).

Compound 24d was prepared from 15 (404 mg, 1.0 mmol) and thio-

phene-3-boronic acid (192 mg, 1.5 mmol) by GPA′. Column chroma-

tography (hexanes/EtOAc 2:1) gave the product (358 mg, 99%) as a

yellowish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 2.58 (s, 3 H, CH₃-2), 3.58 (m, 2 H, OCH₂CH₂Si), 5.57 (s, 2 H,

NCH₂O), 5.63 (bs, 2 H, NH₂), 7.06 (s, 1 H, H-6), 7.22 (dd, J_4,5= 4.9 Hz, J_4,5

= 1.3 Hz, 1 H, H-4-thienyl), 7.31 (dd, J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-

thienyl), 7.46 (dd, J_5,4= 4.9 Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.69 (OCH₂CH₂Si),

25.05 (CH₃-2), 66.41 (OCH₂CH₂Si), 72.58 (NCH₂O), 98.90 (C-4a),

112.06 (C-5), 122.03 (CH-2-thienyl), 122.21 (CH-6), 127.04 (CH-5-

thienyl), 128.37 (CH-4-thienyl), 134.78 (C-3-thienyl), 151.87 (C-7a),

156.26 (C-4), 160.40 (C-2).

MS (ESI): m/z (%) = 345.2 (100) [M + H], 367.2 (10) [M + Na].

MS (ESI): m/z (%) = 361.2 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅O₂N₄Si: 345.1741; found:

345.1742.

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅ON₄SSi: 361.1513; found:

361.1514.

4-Amino-5-(furan-3-yl)-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24b)

4-Amino-5-(benzofuran-2-yl)-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24e)

Compound 24b was prepared from 15 (404 mg, 1.0 mmol) and furan-

3-boronic acid (168 mg, 1.5 mmol) by GPA′. Column chromatography

(hexanes/EtOAc 2:1) gave the product (302 mg, 88%) as a yellowish

oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃-2), 3.57 (m, 2 H, OCH₂CH₂Si), 5.55 (s, 2 H,

NCH₂O), 6.57 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.00 (s, 1 H,

H-6), 7.54 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 7.57 (dd, J_2,5= 1.6 Hz,

J_2,4= 0.9 Hz, 1 H, H-2-furyl).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.47 (CH₃Si), 17.67 (OCH₂CH₂Si),

25.57 (CH₃-2), 66.29 (OCH₂CH₂Si), 72.44 (NCH₂O), 99.28 (C-4a),

106.88 (C-5), 111.52 (CH-4-furyl), 118.94 (C-3-furyl), 121.97 (CH-6),

139.55 (CH-2-furyl), 143.90 (CH-5-furyl), 152.40 (C-7a), 156.81 (C-4),

161.42 (C-2).

Compound 24e was prepared from 15 (404 mg, 1.0 mmol) and benzo-

furan-2-boronic acid (243 mg, 1.5 mmol) by GPA′. Column chroma-

tography (hexanes/EtOAc 2:1) gave the product (355 mg, 90%) as a

white needles.

¹H NMR (500 MHz, CDCl₃): δ = –0.03 (s, 9 H, CH₃Si), 0.95 (m, 2 H,

OCH₂CH₂Si), 2.59 (s, 3 H, CH₃-2), 3.59 (m, 2 H, OCH₂CH₂Si), 5.60 (s, 2 H,

NCH₂O), 6.16 (bs, 2 H, NH₂), 6.85 (d, J_3,7= 0.9 Hz, 1 H, H-3-benzofuryl),

7.24–7.31 (m, 2 H, H-5,6-benzofuryl), 7.45 (s, 1 H, H-6), 7.52 (m, 1 H,

H-7-benzofuryl), 7.57 (m, 1 H, H-4-benzofuryl).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.47 (CH₃Si), 17.69 (OCH₂CH₂Si),

25.66 (CH₃-2), 66.51 (OCH₂CH₂Si), 72.67 (NCH₂O), 97.72 (C-4a),

101.36 (CH-3-benzofuryl), 106.74 (C-5), 110.79 (CH-7-benzofuryl),

120.60 (CH-4-benzofuryl), 122.81 (CH-6), 123.47 and 123.88 (CH-5,6-

benzofuryl), 129.02 (C-3a-benzofuryl), 151.38 (C-2-benzofuryl),

152.88 (C-7a), 154.21 (C-7a-benzofuryl), 156.92 (C-4), 162.05 (C-2).

MS (EI): m/z (%) = 344.2 (100).

HRMS (EI): m/z [M] calcd for

C₁₇H₂₄N₄O₂Si: 344.1671; found:

MS (EI): m/z (%) = 394.2 (100).

344.1669.

I

N. Sabat et al.

Special Topic

Synthesis

HRMS (EI): m/z [M] calcd for C₂₁H₂₆N₄O₂Si: 394.1824; found:

J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.67 (dd, J_5,4= 1.8 Hz, J_5,3= 0.9

394.1825.

Hz, 1 H, H-5-furyl), 7.84 (s, 1 H, H-6), 8.50 (s, 1 H, H-2).

¹³C NMR (101 MHz, CDCl₃): δ = –1.45 (CH₃Si), 17.72 (OCH₂CH₂Si),

53.80 (CH₃O), 66.50 (OCH₂CH₂Si), 73.15 (NCH₂O), 101.87 (C-4a),

107.34 (C-5), 108.34 (CH-3-furyl), 111.45 (CH-4-furyl), 122.20 (CH-

6), 140.91 (CH-5-furyl), 148.70 (C-2-furyl), 151.61 (CH-2), 152.79 (C-

7a), 163.27 (C-4).

4-Amino-5-(dibenzo[b,d]furan-4-yl)-2-methyl-7-{[2-(trimethyl-

silyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (24f)

Compound 24f was prepared from 15 (404 mg, 1.0 mmol) and diben-

zo[b,d]furan-4-boronic acid (318 mg, 1.5 mmol) by GPA′. Column

chromatography (hexanes/EtOAc 2:1) gave the product (409 mg, 92%)

as a yellowish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.01 (s, 9 H, CH₃Si), 0.99 (m, 2 H,

OCH₂CH₂Si), 2.61 (s, 3 H, CH₃-2), 3.67 (m, 2 H, OCH₂CH₂Si), 5.08 (bs, 2

H, NH₂), 5.67 (s, 2 H, NCH₂O), 7.38 (btd, J_8,7= J_8,9= 7.5 Hz, J_8,6= 1.1 Hz,

1 H, H-8-C₁₂H₇O), 7.40 (s, 1 H, H-6), 7.45 (t, J_2,3= J_2,1= 7.6 Hz, 1 H, H-2-

MS (EI): m/z (%) = 345.2 (100) [M].

HRMS (EI): m/z [M] calcd for

C₁₇H₂₃N₃O₃Si: 345.1509; found:

345.1512.

5-(Furan-3-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (25b)

C

₁₂H₇O), 7.48 (ddd, J_7,6= 8.3 Hz, J_7,8= 7.3 Hz, J_7,9= 1.3 Hz, 1 H, H-7-

₁₂H₇O), 7.54 (dd, J_3,2= 7.5 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₂H₇O), 7.57 (dt,

Compound 25b was prepared from 9 (600 mg, 1.48 mmol) and furan-

3-boronic acid (183 mg, 1.63 mmol) by GPA′′. Flash column chroma-

tography (0–5% EtOAc/PE) gave the product (455 mg, 89%) as a yel-

lowish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.06 (s, 9 H, CH₃Si), 0.92 (m, 2 H,

OCH₂CH₂Si), 3.54 (m, 2 H, OCH₂CH₂Si), 4.16 (s, 3 H, CH₃O), 5.62 (s, 2 H,

NCH₂O), 6.70 (dd, J_4,5= 1.9 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.30 (s, 1 H,

H-6), 7.46 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 8.00 (dd, J_2,5= 1.6 Hz,

J_2,4= 0.9 Hz, 1 H, H-2-furyl), 8.48 (s, 1 H, H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.71 (OCH₂CH₂Si),

53.72 (CH₃O), 66.44 (OCH₂CH₂Si), 72.94 (NCH₂O), 103.08 (C-4a),

108.43 (C-5), 109.80 (CH-4-furyl), 118.20 (C-3-furyl), 122.36 (CH-6),

140.45 (CH-2-furyl), 142.83 (CH-5-furyl), 151.45 (CH-2), 152.98 (C-

7a), 163.30 (C-4).

J_6,7= 8.3 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₂H₇O), 7.95 (dd, J_1,2= 7.7 Hz,

J_1,3= 1.3 Hz, 1 H, H-1-C₁₂H₇O), 8.00 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6

0.7 Hz, 1 H, H-9-C₁₂H₇O).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.42 (CH₃Si), 17.76 (OCH₂CH₂Si),

25.73 (CH₃-2), 66.46 (OCH₂CH₂Si), 72.75 (NCH₂O), 99.52 (C-4a),

110.26 (C-5), 111.91 (CH-6-C₁₂H₇O), 119.33 (C-4-C₁₂H₇O), 119.58

(CH-1-C₁₂H₇O), 120.85 (CH-9-C₁₂H₇O), 123.01 (CH-8-C₁₂H₇O), 123.34

(CH-2-C₁₂H₇O), 123.96 (CH-6), 124.21 (C-9a-C₁₂H₇O), 124.94 (C-9b-

=

C

₁₂H₇O), 127.50 (CH-7-C₁₂H₇O), 127.90 (CH-3-C₁₂H₇O), 152.70 (C-7a),

153.64 (C-4a-C₁₂H₇O), 156.16 (C-5a-C₁₂H₇O), 156.93 (C-4), 161.57 (C-

2).

MS (ESI): m/z (%) = 445.2 (100) [M + H], 467.2 (5) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₅H₂₉O₂N₄Si: 445.2054; found:

445.2055.

MS (ESI): m/z (%) = 346.2 (23) [M + H], 368.1 (77) [M + Na].

HRMS (EI): m/z [M + Na] calcd for C₁₇H₂₃O₃N₃NaSi: 368.1400; found:

368.1399.

4-Amino-2-methyl-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (24g)

4-Methoxy-5-(thiophen-2-yl)-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (25c)

Compound 24g was prepared from 15 (404 mg, 1.0 mmol) and phen-

ylboronic acid (183 mg, 1.5 mmol) by GPA′. Column chromatography

(hexanes/EtOAc 2:1) gave the product (350 mg, 98%) as a yellowish

oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.03 (s, 9 H, CH₃Si), 0.95 (m, 2 H,

OCH₂CH₂Si), 2.59 (s, 3 H, CH₃-2), 3.59 (m, 2 H, OCH₂CH₂Si), 5.16 (bs, 2

H, NH₂), 5.59 (s, 2 H, NCH₂O), 7.03 (s, 1 H, H-6), 7.36 (m, 1 H, H-p-Ph),

7.45 (m, 2 H, H-m-Ph), 7.49 (m, 2 H, H-o-Ph).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.71 (OCH₂CH₂Si),

25.55 (CH₃-2), 66.34 (OCH₂CH₂Si), 72.58 (NCH₂O), 98.80 (C-4a),

117.35 (C-5), 121.97 (CH-6), 127.23 (CH-p-Ph), 128.71 (CH-o-Ph),

129.02 (CH-m-Ph), 134.77 (C-i-Ph), 152.48 (C-7a), 156.68 (C-4),

161.29 (C-2).

Compound 25c was prepared from 9 (500 mg, 1.23 mmol) and 2-

(tributylstannyl)thiophene (0.46 mL, 1.48 mmol) by GPB. Flash col-

umn chromatography (0–5% EtOAc/PE) provided a brownish oil (369

mg, 83%).

¹H NMR (400 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.55 (m, 2 H, OCH₂CH₂Si), 4.08 (s, 3 H, CH₃O), 5.61 (s, 2 H,

NCH₂O), 7.11 (dd, J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1 H, H-4-thienyl), 7.45 (dd,

J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.48 (dd, J_3,4= 3.6 Hz, J_3,5

1.2 Hz, 1 H, H-3-thienyl), 7.84 (s, 1 H, H-6), 8.50 (s, 1 H, H-2).

=

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.94 (CH₃Si), 17.55 (OCH₂CH₂Si),

54.11 (CH₃O) , 66.18 (OCH₂CH₂Si), 73.07 (NCH₂O), 102.38 (C-4a),

109.88 (C-5), 124.88 (CH-6), 125.46 (CH-5-thienyl), 126.17 (CH-3-

thienyl), 128.18 (CH-4-thienyl), 135.86 (C-2-thienyl), 151.78 (CH-2),

152.84 (C-7a), 163.10 (C-4).

MS (ESI): m/z (%) = 355.2 (100) [M + H], 377.2 (5) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₉H₂₇ON₄Si: 355.1949; found:

355.1950.

MS (EI): m/z (%) = 361.1 (100) [M].

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃O₂SiS: 361.1280; found:

361.1284.

5-(Furan-2-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (25a)

Compound 25a was prepared from 9 (500 mg, 1.23 mmol) and 2-

(tributylstannyl)furan (0.32 mL, 1.48 mmol) by GPB. Flash column

chromatography (0–5% EtOAc/PE) gave the product (338 mg, 80%) as a

greenish oil.

¹H NMR (400 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.54 (m, 2 H, OCH₂CH₂Si), 4.12 (s, 3 H, CH₃O), 5.62 (s, 2 H,

NCH₂O), 6.57 (dd, J_4,3= 3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 6.94 (dd,

4-Methoxy-5-(thiophen-3-yl)-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (25d)

Compound 25d was prepared from 9 (700 mg, 1.73 mmol) and thio-

phene-3-boronic acid (245 mg, 1.90 mmol) by GPA′′. Flash column

chromatography (0–5% EtOAc/PE) gave the product (612 mg, 98%) as a

yellowish oil.

J

N. Sabat et al.

Special Topic

Synthesis

¹H NMR (400 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.85 (m, 2 H,

OCH₂CH₂Si), 3.54 (m, 2 H, OCH₂CH₂Si), 4.10 (s, 3 H, CH₃O), 5.61 (s, 2 H,

NCH₂O), 7.54 (dd, J_4,5= 5.0 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.58 (dd,

HRMS (ESI): m/z [M + Na] calcd for C₂₅H₂₇O₃N₃NaSi: 468.1713; found:

468.1714.

J_5,4= 5.0 Hz, J_5,2= 2.9 Hz, 1 H, H-5-thienyl), 7.87 (dd, J_2,5= 2.7 Hz, J_2,4

1.5 Hz, 1 H, H-2-thienyl), 7.92 (s, 1 H, H-6), 8.48 (s, 1 H, H-2).

=

4-Methoxy-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidine (25g)

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.94 (CH₃Si), 17.55 (OCH₂CH₂Si),

54.16 (CH₃O), 66.13 (OCH₂CH₂Si), 73.05 (NCH₂O), 102.58 (C-4a),

111.70 (C-5), 121.71 (CH-2-thienyl), 125.62 (CH-6), 126.25 (CH-5-

thienyl), 128.20 (CH-4-thienyl), 134.27 (C-3-thienyl), 151.49 (CH-2),

152.93 (C-7a), 163.10 (C-4).

Compound 25g was prepared from 9 (450 mg, 1.11 mmol) and phen-

ylboronic acid (154 mg, 1.26 mmol) by GPA′′. Flash column chroma-

tography (0–5% EtOAc/PE) gave the product (330 mg, 84%) as a color-

less oil.

¹H NMR (400 MHz, CDCl₃): δ = –0.02 (s, 9 H, CH₃Si), 0.97 (m, 2 H,

OCH₂CH₂Si), 3.61 (m, 2 H, OCH₂CH₂Si), 4.12 (s, 3 H, CH₃O), 5.69 (s, 2 H,

NCH₂O), 7.31 (s, 1 H, H-6), 7.35 (m, 1 H, H-p-Ph), 7.44 (m, 2 H, H-m-

Ph), 7.69 (m, 2 H, H-o-Ph), 8.54 (s, 1 H, H-2).

MS (EI): m/z (%) = 361.1 (100) [M].

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃O₂SiS: 361.1280; found:

361.1281.

¹³C NMR (101 MHz, CDCl₃): δ = –1.42 (CH₃Si), 17.76 (OCH₂CH₂Si),

53.71 (CH₃O), 66.53 (OCH₂CH₂Si), 73.09 (NCH₂O), 103.38 (C-4a),

117.98 (C-5), 123.56 (CH-6), 126.70 (CH-p-Ph), 128.20 (CH-m-Ph),

128.80 CH-o-Ph), 133.89 (C-i-Ph), 151.29 (CH-2), 153.03 (C-7a),

163.51 (C-4).

5-(Benzofuran-2-yl)-4-methoxy-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (25e)

Compound 25e was prepared from 9 (700 mg, 1.73 mmol) and benzo-

furan-2-boronic acid (308 mg, 1.90 mmol) by GPA′′. Flash column

chromatography (0–5% EtOAc/PE) gave the product (627 mg, 92%) as a

yellowish powder.

MS (EI): m/z (%) = 355.2 (100) [M], 356.2 (10) [M + H].

HRMS (EI): m/z [M] calcd for

C₁₉H₂₅N₃O₂Si: 355.1716; found:

¹H NMR (400 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

355.1718.

OCH₂CH₂Si), 3.58 (m, 2 H, OCH₂CH₂Si), 4.19 (s, 3 H, CH₃O), 5.67 (s, 2 H,

NCH₂O), 7.27 (m, 2 H, H-5-benzofuryl, H-6-benzofuryl), 7.43 (d, J_3,7

=

5-(Furan-2-yl)-4-(methylsulfanyl)-7-{[2-(trimethylsilyl)-

0.8 Hz, 1 H, H-3-benzofuryl), 7.56 (m, 1 H, H-7-benzofuryl), 7.66

(ddd, J_4,5= 7.3 Hz, J_4,6= 1.6 Hz, J_4,7= 0.7 Hz, 1 H, H-4-benzofuryl), 8.13

(s, 1 H, H-6), 8.55 (s, 1 H, H-2).

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.94 (CH₃Si), 17.58 (OCH₂CH₂Si),

54.49 (CH₃O), 66.30 (OCH₂CH₂Si), 73.37 (NCH₂O), 101.73 (C-4a),

103.56 (CH-3-benzofuryl), 106.36 (C-5), 110.98 (CH-7-benzofuryl),

121.32 (CH-4-benzofuryl), 123.46 (CH-6-benzofuryl), 124.53 (CH-6),

126.28 (CH-5-benzofuryl), 129.67 (C-3a-benzofuryl), 150.91 (C-2-

benzofuryl), 152.31 (CH-2), 153.22 (C-7a), 154.05 (C-7a-benzofuryl),

163.09 (C-4).

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26a)

Compound 26a was prepared from 10 (700 mg, 1.66 mmol) and 2-

(tributylstannyl)furan (0.43 mL, 1.99 mmol) by GPB. Flash column

chromatography (0–5% EtOAc/PE) gave the product (492 mg, 82%) as a

brown oil.

¹H NMR (401 MHz, CDCl₃): δ = –0.02 (s, 9 H, CH₃Si), 0.95 (m, 2 H,

OCH₂CH₂Si), 2.68 (s, 3 H, CH₃S), 3.59 (m, 2 H, OCH₂CH₂Si), 5.66 (s, 2 H,

NCH₂O), 6.54 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 6.74 (dd,

J_3,4= 3.3 Hz, J_3,5= 0.7 Hz, 1 H, H-3-furyl), 7.46 (s, 1 H, H-6), 7.56 (dd, J_5,4

= 1.8 Hz, J_5,3= 0.8 Hz, 1 H, H-5-furyl), 8.71 (s, 1 H, H-2).

MS (EI): m/z (%) = 395.2 (100) [M], 396.2 (10) [M + H].

¹³C NMR (101 MHz, CDCl₃): δ = –1.42 (CH₃Si), 12.63 (CH₃S), 17.74

(OCH₂CH₂Si), 66.68 (OCH₂CH₂Si), 72.95 (NCH₂O), 107.87 (C-5), 109.05

(CH-3-furyl), 111.27 (CH-4-furyl), 113.82 (C-4a), 125.73 (CH-6),

142.06 (CH-5-furyl), 147.13 (C-2-furyl), 149.29 (C-7a), 151.14 (CH-2),

162.62 (C-4).

HRMS (EI): m/z [M] calcd for

C₂₁H₂₅N₃O₃Si: 395.1665; found:

395.1663.

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (25f)

MS (EI): m/z (%) = 361.1 (100) [M], 362.1 (10) [M + H].

Compound 25f was prepared from 9 (700 mg, 1.73 mmol) and diben-

zo[b,d]furan-4-boronic acid (405 mg, 1.90 mmol) by GPA′′. Flash col-

umn chromatography (0–5% EtOAc/PE) gave the product (725 mg,

94%) as a yellowish oil.

¹H NMR (400 MHz, CDCl₃): δ = 0.01 (s, 9 H, CH₃Si), 1.04–0.98 (m, 2 H,

OCH₂CH₂Si), 3.72–3.66 (m, 2 H, OCH₂CH₂Si), 4.09 (s, 3 H, CH₃O), 5.78

(s, 2 H, NCH₂O), 7.39 (btd, J_8,9= J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃O₂SiS: 361.1280; found:

361.1281.

5-(Furan-3-yl)-4-(methylsulfanyl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26b)

Compound 26b was prepared from 10 (500 mg, 1.19 mmol) and fu-

ran-3-boronic acid (147 mg, 1.35 mmol) by GPA′′. Flash column chro-

matography (0–5% EtOAc/PE) gave the product (395 mg, 93%) as a yel-

lowish oil.

¹H NMR (400 MHz, DMSO-d₆): δ = –0.08 (s, 9 H, CH₃Si), 0.85 (m, 2 H,

OCH₂CH₂Si), 2.59 (s, 3 H, CH₃S), 3.55 (m, 2 H, OCH₂CH₂Si), 5.61 (s, 2 H,

NCH₂O), 7.69 (s, 1 H, H-6), 6.73 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-

furyl), 7.77 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 7.88 (dd, J_2,5= 1.6 Hz,

J_2,4= 0.8 Hz, 1 H, H-2-furyl), 8.68 (s, 1 H, H-2).

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.93 (CH₃Si), 12.31 (CH₃S), 17.56

(OCH₂CH₂Si), 66.22 (OCH₂CH₂Si), 72.82 (NCH₂O), 106.98 (C-5), 113.27

(CH-4-furyl), 114.34 (C-4a), 117.88 (C-3-furyl), 127.50 (CH-6), 141.14

(CH-2-furyl), 143.53 (CH-5-furyl), 149.29 (C-7a), 151.08 (CH-2),

161.62 (C-4).

C

₁₀H₇O), 7.51–7.43 (m, 2 H, H-2-C₁₀H₇O, H-7-C₁₀H₇O), 7.61 (dt, J = 8.3,

0.9 Hz, J_6,7= 8.3 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₀H₇O), 7.91 (s, 1 H, H-

6), 7.94 (m, 2 H, H-1-C₁₀H₇O, H-3-C₁₀H₇O), 8.01 (ddd, J_9,8= 7.7 Hz, J_9,7

1.4 Hz , J_9,6= 0.7 Hz, 1 H, H-9-C₁₀H₇O), 8.59 (s, 1 H, H-2).

=

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.91 (CH₃Si), 17.64 (OCH₂CH₂Si),

54.09 (CH₃O), 66.31 (OCH₂CH₂Si), 73.28 (NCH₂O), 103.67 (C-4a),

109.89 (C-5), 112.02 (CH-6-C₁₀H₇O), 118.86 (CH-1-C₁₀H₇O), 119.86

(C-4-C₁₀H₇O), 121.68 (CH-9-C₁₀H₇O), 123.42 (CH-2-C₁₀H₇O), 123.55

(CH-8-C₁₀H₇O), 124.09 (C-9b-C₁₀H₇O), 124.23 (C-9a-C₁₀H₇O), 127.80

(CH-6), 128.00 (CH-7-C₁₀H₇O), 129.19 (CH-3-C₁₀H₇O), 151.64 (CH-2),

152.85 (C-7a), 153.52 (C-4a-C₁₀H₇O), 155.85 (C-5a-C₁₀H₇O), 163.26

(C-4).

MS (ESI): m/z (%) = 446.2 (53) [M + H], 468.2 (47) [M + Na].

K

N. Sabat et al.

Special Topic

Synthesis

MS (EI): m/z (%) = 361.1 (100) [M], 362.1 (10) [M + H].

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.20 (CH₃Si), 12.44 (CH₃S),

17.33 (OCH₂CH₂Si), 66.18 (OCH₂CH₂Si), 72.97 (NCH₂O), 104.98 (CH-3-

benzofuryl), 105.81 (C-5), 111.12 (CH-7-benzofuryl), 113.12 (C-4a),

121.17 (CH-4-benzofuryl), 123.27 (CH-5-benzofuryl), 124.45 (CH-6-

benzofuryl), 129.00 (C-3a-benzofuryl), 129.18 (CH-6), 149.31 (C-7a),

149.74 (C-2-benzofuryl), 151.33 (CH-2), 154.29 (C-7a-benzofuryl),

161.93 (C-4).

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃O₂SiS: 361.1280; found:

361.1281.

4-(Methylsulfanyl)-5-(thiophen-2-yl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26c)

Compound 26c was prepared from 10 (700 mg, 1.66 mmol) and 2-

(tributylstannyl)thiophene (0.62 mL, 1.99 mmol) by GPB. Flash col-

umn chromatography (0–5% EtOAc/PE) gave the product (474 mg,

76%) as a brown oil.

MS (EI): m/z (%) = 411.1 (100) [M], 412.1 (10) [M + H].

HRMS (EI): m/z [M] calcd for C₂₁H₂₅N₃O₂SiS: 411.1437; found:

411.1440.

¹H NMR (400 MHz, DMSO-d₆): δ = –0.08 (s, 9 H, CH₃Si), 0.85 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃S), 3.59 (m, 2 H, OCH₂CH₂Si), 5.63 (s, 2 H,

NCH₂O), 7.16 (dd, J_4,5= 5.2 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.23 (dd,

5-(Dibenzo[b,d]furan-4-yl)-4-(methylsulfanyl)-7-{[2-(trimethyl-

silyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26f)

J_3,4= 3.6 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl), 7.59 (dd, J_5,4= 5.2 Hz, J_5,3

1.2 Hz, 1 H, H-5-thienyl), 7.79 (s, 1 H, H-6), 8.71 (s, 1 H, H-2).

=

Compound 26f was prepared from 10 (550 mg, 1.30 mmol) and

dibenzo[b,d]furan-4-boronic acid (303 mg, 1.43 mmol) by GPA′′. Flash

column chromatography (0–5% EtOAc/PE) gave the product (598 mg,

99%) as a yellow oil.

¹H NMR (400 MHz, CDCl₃): δ = 0.02 (s, 9 H, CH₃Si), 1.01 (m, 2 H,

OCH₂CH₂Si), 2.53 (s, 3 H, CH₃S), 3.69 (m, 2 H, OCH₂CH₂Si), 7.39 (btd,

J_8,9= J_8,7= 7.6 Hz, J_8,6= 0.9 Hz, 1 H, H-8-C₁₀H₇O), 7.47 (m, 2 H, H-2-

¹³C NMR (101 MHz, DMSO-d₆): δ = –0.92 (CH₃Si), 12.32 (CH₃S), 17.57

(OCH₂CH₂Si), 66.32 (OCH₂CH₂Si), 72.96 (NCH₂O), 108.87 (C-4a),

114.34 (C-5), 126.72 (CH-6), 127.93 (CH-5-thienyl), 128.71 (CH-3-

thienyl), 128.99 (CH-4-thienyl), 134.16 (C-2-thienyl), 149.08 (CH-2),

151.30 (C-7a), 161.88 (C-4).

C

₁₀H₇O and H-7-C₁₀H₇O), 7.53 (s, 1 H, H-6), 7.61 (bdt, J_6,7= 8.0 Hz, J_6,8=

MS (EI): m/z (%) = 377.1 (100) [M], 378.1 (10) [M + H].

J_6,9= 1.0 Hz, 1 H, H-6-C₁₀H₇O), 7.61 (dd, J_3,2= 7.7 Hz, J_3,1= 1.4 Hz, 1 H,

H-3-C₁₀H₇O), 8.03 (m, 2 H, H-1-C₁₀H₇O, H-9-C₁₀H₇O), 8.78 (s, 1 H, H-

2).

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃OSiS₂: 377.1052; found:

377.1053.

¹³C NMR (101 MHz, CDCl₃): δ = –1.35 (CH₃Si), 12.43 (CH₃S), 17.82

(OCH₂CH₂Si), 66.77 (OCH₂CH₂Si), 73.11 (NCH₂O), 111.33 (C-5), 111.87

(CH-6-C₁₀H₇O), 115.45 (C-4a), 118.31 (C-4-C₁₀H₇O), 120.09 (CH-1-

4-(Methylsulfanyl)-5-(thiophen-3-yl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26d)

Compound 26d was prepared from 10 (700 mg, 1.66 mmol) and thio-

phene-3-boronic acid (255 mg, 1.82 mmol) by GPA′′. Flash column

chromatography (0–5% EtOAc/PE) gave the product (584 mg, 93%) as a

straw oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃S), 3.55 (m, 2 H, OCH₂CH₂Si), 5.61 (s, 2 H,

NCH₂O), 7.28 (dd, J_4,5= 4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.56 (dd,

C

₁₀H₇O), 120.79 (CH-9-C₁₀H₇O), 122.44 (CH-2-C₁₀H₇O), 122.81 (CH-8-

₁₀H₇O), 124.25 (C-9b-C₁₀H₇O), 124.45 (C-9a-C₁₀H₇O), 126.42 (CH-6),

127.20 (CH-7-C₁₀H₇O), 129.88 (CH-3-C₁₀H₇O), 149.27 (C-7a), 151.07

(CH-2), 154.63 (C-4a-C₁₀H₇O), 156.20 (C-5a-C₁₀H₇O), 162.84 (C-4).

MS (EI): m/z (%) = 461.1 (100) [M], 462.1 (10) [M + H].

HRMS (EI): m/z [M] calcd for C₂₅H₂₇N₃O₂SSi: 461.1593; found:

461.1595.

J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.62 (dd, J_5,4= 4.9 Hz, J_5,2

=

3.0 Hz, 1 H, H-5-thienyl), 7.70 (s, 1 H, H-6), 8.67 (s, 1 H, H-2).

4-(Methylsulfanyl)-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (26g)

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.17 (CH₃Si), 12.12 (CH₃S),

17.32 (OCH₂CH₂Si), 66.00 (OCH₂CH₂Si), 72.63 (NCH₂O), 111.33 (C-5),

114.01 (C-4a), 124.02 (CH-2-thienyl), 125.79 (CH-5-thienyl), 127.31

(CH-6), 130.01 (CH-4-thienyl), 133.48 (C-3-thienyl), 148.84 (C-7a),

150.80 (CH-2), 161.41 (C-4).

Compound 26g was prepared from 10 (300 mg, 0.72 mmol) and

phenylboronic acid (154 mg, 1.08 mmol) by GPA′′. Thecrude yellow-

ish oil (251 mg, 94%) obtained was used in the next step without ad-

ditional purification.

MS (EI): m/z (%) = 377.1 (100) [M], 378.1 (10) [M + H].

MS (ESI): m/z (%) = 394.1 (100) [M + Na].

HRMS (EI): m/z [M] calcd for C₁₇H₂₃N₃OSiS₂: 377.1052; found:

377.1058.

HRMS (ESI): m/z [M + Na] calcd for C₁₉H₂₅ON₃NaSSi: 394.1379; found:

394.1380.

5-(Benzofuran-2-yl)-4-(methylsulfanyl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (26e)

5-(Furan-2-yl)-4-methyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidine (27a)

Compound 26e was prepared from 10 (500 mg, 1.19 mmol) and ben-

zofuran-2-boronic acid (218 mg, 1.35 mmol) by GPA′′. Flash column

chromatography (0–5% EtOAc/PE) gave the product (425 mg, 87%) as a

yellow oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.61 (s, 3 H, CH₃S), 3.57 (m, 2 H, OCH₂CH₂Si), 5.67 (s, 2 H,

Compound 27a was prepared from 12 (200 mg, 0.51 mmol) and fu-

ran-2-boronic acid (72 mg, 0.64 mmol) by GPA′′′. Column chromatog-

raphy (silica gel, hexane/EtOAc 10:1) gave the product (153 mg, 91%)

as a yellowish amorphous solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 2.76 (s, 3 H, CH₃-4), 3.56 (m, 2 H, OCH₂CH₂Si), 5.66 (s, 2 H,

NCH₂O), 6.49 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 6.51 (dd,

NCH₂O), 7.23 (d, J_3,7= 0.9 Hz, 1 H, H-3-benzofuryl), 7.26 (btd, J_5,6

=

J_5,4= 7.4 Hz, J_5,7= 1.1 Hz, 1 H, H-5-benzofuryl), 7.31 (bddd, J_6,7= 8.1 Hz,

J_6,5= 7.2 Hz, J_6,4= 1.5 Hz, 1 H, H-6-benzofuryl), 7.59 (m, 1 H, H-7-ben-

zofuryl), 7.68 (m, 1 H, H-4-benzofuryl), 8.13 (s, 1 H, H-6), 8.73 (s, 1 H,

H-2).

J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 7.47 (s, 1 H, H-6), 7.54 (dd, J_5,4

1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 8.79 (s, 1 H, H-2).

=

L

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.47 (CH₃Si), 17.70 (OCH₂CH₂Si),

23.22 (CH₃-4), 66.69 (OCH₂CH₂Si), 72.77 (NCH₂O), 107.89 (C-5),

108.10 (CH-3-furyl), 111.25 (CH-4-furyl), 115.59 (C-4a), 126.58 (CH-

6), 142.18 (CH-5-furyl), 147.82 (C-2-furyl), 151.24 (C-7a), 151.87

(CH-2), 160.56 (C-4).

J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.29 (s, 1 H, H-6), 7.42 (dd,

J_5,4= 4.9 Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl), 8.78 (s, 1 H, H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.70 (OCH₂CH₂Si),

22.79 (CH₃-4), 66.61 (OCH₂CH₂Si), 72.65 (NCH₂O), 112.71 (C-5),

116.42 (C-4a), 123.29 (CH-2-thienyl), 125.51 (CH-5-thienyl), 126.00

(CH-6), 129.57 (CH-4-thienyl), 134.30 (C-3-thienyl), 151.10 (C-7a),

151.65 (CH-2), 160.11 (C-4).

MS (ESI): m/z (%) = 330.2 (100) [M + H], 352.2 (13) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₄O₂N₃Si: 330.16323; found:

330.16336.

MS (ESI): m/z (%) = 346.1 (100) [M + H], 368.1 (9) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₄ON₃SSi: 346.14039; found:

346.14044.

5-(Furan-3-yl)-4-methyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidine (27b)

Compound 27b was prepared from 12 (200 mg, 0.51 mmol) and fu-

ran-3-boronic acid (72 mg, 0.64 mmol) by GPA′′′. Column chromatog-

raphy (silica gel, hexane/EtOAc 10:1) gave the product (167 mg, 99%)

as a white amorphous solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 2.66 (s, 3 H, CH₃-4), 3.56 (m, 2 H, OCH₂CH₂Si), 5.65 (s, 2 H,

NCH₂O), 7.55 (dd, J_4,5= 1.8 Hz, J_4,2= 1.0 Hz, 1 H, H-4-furyl), 7.26 (s, 1 H,

H-6), 7.52–7.54 (m, 2 H, H-2,5-furyl), 8.78 (s, 1 H, H-2).

5-(Benzofuran-2-yl)-4-methyl-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidine (27e)

Compound 27e was prepared from 12 (200 mg, 0.51 mmol) and ben-

zofuran-2-boronic acid (104 mg, 0.64 mmol) by GPA′′′. Purification by

HPFC (silica gel, gradient 0–100% EtOAc/hexane) gave the product

(164 mg, 84%) as a beige amorphous solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.95 (m, 2 H,

OCH₂CH₂Si), 2.88 (s, 3 H, CH₃-4), 3.59 (m, 2 H, OCH₂CH₂Si), 5.71 (s, 2 H,

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.47 (CH₃Si), 17.69 (OCH₂CH₂Si),

22.65 (CH₃-4), 66.60 (OCH₂CH₂Si), 72.62 (NCH₂O), 108.10 (C-5),

112.69 (CH-4-furyl), 116.51 (C-4a), 118.27 (C-3-furyl), 126.10 (CH-6),

140.29 (CH-2-furyl), 143.07 (CH-5-furyl), 151.31 (C-7a), 151.60 (CH-

2), 160.04 (C-4).

NCH₂O), 6.88 (d, J_3,7= 1.0 Hz, 1 H, H-3-benzofuryl), 7.27 (td, J_5,6= J_5,4

7.4 Hz, J_5,7= 1.1 Hz, 1 H, H-5-benzofuryl), 7.21 (bddd, J_6,7= 8.0 Hz, J_6,5

7.2 Hz, J_6,4= 1.5 Hz, 1 H, H-6-benzofuryl), 7.53 (dq, J_7,6= 8.0 Hz, J_7,5

J_7,4= J_7,3= 1.0 Hz, 1 H, H-7-benzofuryl), 7.62 (ddd, J_4,5= 7.5 Hz, J_4,6= 1.5

Hz, J_4,7= 0.8 Hz, 1 H, H-4-benzofuryl), 7.67 (s, 1 H, H-6), 8.83 (s, 1 H,

H-2).

=

MS (ESI): m/z (%) = 330.0 (100) [M + H], 352.2 (12) [M + Na].

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.71 (OCH₂CH₂Si),

23.69 (CH₃-4), 66.82 (OCH₂CH₂Si), 72.90 (NCH₂O), 104.30 (CH-3-ben-

zofuryl), 107.60 (C-5), 111.02 (CH-7-benzofuryl), 115.46 (C-4a),

120.73 (CH-4-benzofuryl), 123.03 (CH-5-benzofuryl), 124.16 (CH-6-

benzofuryl), 127.71 (CH-6), 128.93 (C-3a-benzofuryl), 150.36 (C-2-

benzofuryl), 151.49 (C-7a), 152.06 (CH-2), 154.80 (C-7a-benzofuryl),

160.67 (C-4).

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₄O₂N₃Si: 330.16323; found:

330.16330.

4-Methyl-5-(thiophen-2-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (27c)

Compound 27c was prepared from 12 (200 mg, 0.51 mmol) and thio-

phene-2-boronic acid (82 mg, 0.64 mmol) by GPA′′′. Column chroma-

tography (silica gel, hexane/EtOAc 10:1) gave the product (172 mg,

98%) as a yellowish oil.

MS (ESI): m/z (%) = 380.2 (100) [M + H], 402.1 (66) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₁H₂₆O₂N₃Si: 380.17888; found:

380.17902.

¹H NMR (500 MHz, CDCl₃): δ = –0.04 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 2.63 (s, 3 H, CH₃-4), 3.58 (m, 2 H, OCH₂CH₂Si), 5.66 (s, 2 H,

NCH₂O), 7.10 (dd, J_3,4= 3.5 Hz, J_3,5= 1.3 Hz, 1 H, H-3-thienyl), 7.11 (dd,

5-(Dibenzo[b,d]furan-4-yl)-4-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (27f)

J_4,5= 5.1 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.36 (dd, J_5,4= 5.1 Hz, J_5,3

=

1.3 Hz, 1 H, H-5-thienyl), 7.36 (s, 1 H, H-6), 8.80 (s, 1 H, H-2).

Compound 27f was prepared from 12 (200 mg, 0.51 mmol) and

dibenzo[b,d]furan-4-boronic acid (136 mg, 0.64 mmol) by GPA′′′. Pu-

rification by HPFC (silica gel, gradient 0–100% EtOAc/hexane) gave the

product (174 mg, 79%) as a yellow oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.02 (s, 9 H, CH₃Si), 0.97 (m, 2 H,

OCH₂CH₂Si), 2.40 (s, 3 H, CH₃-4), 3.66 (m, 2 H, OCH₂CH₂Si), 5.75 (s, 2 H,

NCH₂O), 7.38 (ddd, J_8,9= 7.7 Hz, J_8,7= 7.1 Hz, J_8,6= 1.2 Hz, 1 H, H-8-

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.70 (OCH₂CH₂Si),

22.78 (CH₃-4), 66.71 (OCH₂CH₂Si), 72.72 (NCH₂O), 110.14 (C-5),

116.49 (C-4a), 125.66 (CH-5-thienyl), 127.29 (CH-6, CH-4-thienyl),

127.94 (CH-3-thienyl), 134.97 (C-2-thienyl), 151.05 (C-7a), 151.80

(CH-2), 160.34 (C-4).

MS (ESI): m/z (%) = 346.0 (100) [M + H], 368.0 (17) [M + Na].

C

₁₀H₇O), 7.44 (t, J_2,1= J_2,3= 7.5 Hz, 1 H, H-2-C₁₀H₇O), 7.46 (ddd, J_7,6= 8.2

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₄ON₃SSi: 346.14039; found:

346.14045.

Hz, J_7,8= 7.1 Hz, J_7,9= 1.3 Hz, 1 H, H-7-C₁₀H₇O), 7.49 (dd, J_3,2= 7.4 Hz,

J_3,1= 1.4 Hz, 1 H, H-3-C₁₀H₇O), 7.51 (bdt, J_6,7= 8.3 Hz, J_6,8= J_6,9= 1.0 Hz,

1 H, H-6-C₁₀H₇O), 7.51 (s, 1 H, H-6), 8.00 (dd, J_1,2= 7.6 Hz, J_1,3= 1.4 Hz,

1 H, H-1-C₁₀H₇O), 8.01 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H,

H-9-C₁₀H₇O), 8.55 (s, 1 H, H-2).

4-Methyl-5-(thiophen-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-

7H-pyrrolo[2,3-d]pyrimidine (27d)

Compound 27d was prepared from 12 (200 mg, 0.51 mmol) and thio-

phene-3-boronic acid (82 mg, 0.64 mmol) by GPA′′′. Column chroma-

tography (silica gel, hexane/EtOAc 10:1) gave the product (168 mg,

94%) as a yellowish oil.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.93 (m, 2 H,

OCH₂CH₂Si), 2.58 (s, 3 H, CH₃-4), 3.57 (m, 2 H, OCH₂CH₂Si), 5.66 (s, 2 H,

NCH₂O), 7.18 (dd, J_4,5= 4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.28 (dd,

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.42 (CH₃Si), 17.77 (OCH₂CH₂Si),

22.04 (CH₃-4), 66.76 (OCH₂CH₂Si), 72.92 (NCH₂O), 111.77 (C-5),

111.77 (CH-6-C₁₀H₇O), 116.96 (C-4a), 119.04 (C-4-C₁₀H₇O), 120.08

(CH-1-C₁₀H₇O), 120.83 (CH-9-C₁₀H₇O), 122.87 (CH-2-C₁₀H₇O), 122.98

(CH-8-C₁₀H₇O), 124.27 (C-9a-C₁₀H₇O), 124.42 (C-9b-C₁₀H₇O), 127.02

(CH-6), 127.41 (CH-7-C₁₀H₇O), 129.03 (CH-3-C₁₀H₇O), 151.32 (C-7a),

151.74 (CH-2), 154.33 (C-4a-C₁₀H₇O), 156.04 (C-5a-C₁₀H₇O), 160.60

(C-4).

M

N. Sabat et al.

Special Topic

Synthesis

MS (ESI): m/z (%) = 430.1 (100) [M + H], 452.1 (38) [M + Na].

139.53 (CH-2-furyl), 143.51 (CH-5-furyl), 155.57 (C-7a), 159.93 (C-2),

163.37 (C-4).

HRMS (ESI): m/z [M + H] calcd for C₂₅H₂₈O₂N₃Si: 430.19453; found:

430.19450.

MS (ESI): m/z (%) = 361.2 (100) [M + H], 383.2 (30) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅N₄O₃Si: 361.1690; found:

361.1691.

4-Methyl-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyr-

rolo[2,3-d]pyrimidine (27g)

Compound 27g was prepared from 12 (250 mg, 0.64 mmol) and

phenylboronic acid (98 mg, 0.80 mmol) by GPA′′′. Purification by

HPFC (silica gel, gradient 0–100% EtOAc/hexane) gave the product

(186 mg, 85%) as a white glassy solid.

¹H NMR (500 MHz, CDCl₃): δ = –0.05 (s, 9 H, CH₃Si), 0.94 (m, 2 H,

OCH₂CH₂Si), 2.54 (s, 3 H, CH₃-4), 3.59 (m, 2 H, OCH₂CH₂Si), 5.68 (s, 2

H, NCH₂O), 7.27 (s, 1 H, H-6), 7.39 (m, 1 H, H-p-Ph), 7.41–7.47 (m, 4 H,

H-o,m-Ph), 8.79 (s, 1 H, H-2).

¹³C NMR (125.7 MHz, CDCl₃): δ = –1.46 (CH₃Si), 17.71 (OCH₂CH₂Si),

23.08 (CH₃-4), 66.61 (OCH₂CH₂Si), 72.71 (NCH₂O), 116.23 (C-4a),

118.29 (C-5), 125.82 (CH-6), 127.33 (CH-p-Ph), 128.24 (CH-m-Ph),

129.96 (CH-o-Ph), 134.37 (C-i-Ph), 151.19 (C-7a), 151.59 (CH-2),

160.13 (C-4).

5-(Thiophen-2-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (28c)

Compound 28c was prepared from 13 (420 mg, 1.0 mmol) and thio-

phene-2-boronic acid (192 mg, 1.5 mmol) by GPA′. Flash column

chromatography (30–40% EtOAc/hexanes) gave the product (275 mg,

73%) as a yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.07 (s, 9 H, CH₃Si), 0.83 (m, 2 H,

OCH₂CH₂Si), 3.51 (m, 2 H, OCH₂CH₂Si), 3.96 (s, 3 H, CH₃O-4), 5.37 (s, 2

H, NCH₂O), 6.36 (bs, 2 H, NH₂), 7.04 (dd, J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1 H,

H-4-thienyl), 7.27 (s, 1 H, H-6), 7.34 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H,

H-5-thienyl), 7.40 (dd, J_3,4= 3.6 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.17 (CH₃Si), 17.34 (OCH₂CH₂-

Si), 53.13 (CH₃O-4), 65.43 (OCH₂CH₂Si), 72.25 (NCH₂O), 94.70 (C-4a),

110.01 (C-5), 120.74 (CH-6), 123.57 (CH-5-thienyl), 125.02 (CH-3-

thienyl), 127.76 (CH-4-thienyl), 136.79 (C-2-thienyl), 155.42 (C-7a),

159.95 (C-2), 163.44 (C-4).

MS (ESI): m/z (%) = 340.2 (100) [M + H], 362.2 (20) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₉H₂₆ON₃Si: 340.18397; found:

340.18398.

MS (ESI): m/z (%) = 377.2 (100) [M + H], 399.2 (50) [M + Na].

5-(Furan-2-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]methyl}-

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅N₄O₂SSi: 377.1462; found:

7H-pyrrolo[2,3-d]pyrimidin-2-amine (28a)

377.1462.

Compound 28a was prepared from 13 (420 mg, 1.0 mmol) and furan-

2-boronic acid (168 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (30–40% EtOAc/hexanes) gave the product (256 mg, 71%) as a

yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.08 (s, 9 H, CH₃Si), 0.83 (m, 2 H,

OCH₂CH₂Si), 3.50 (m, 2 H, OCH₂CH₂Si), 3.99 (s, 3 H, CH₃O-4), 5.38 (s, 2

H, NCH₂O), 6.37 (bs, 2 H, NH₂), 6.50 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H,

H-4-furyl), 6.82 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.30 (s, 1

H, H-6), 7.58 (dd, J_5,4= 1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.16 (CH₃Si), 17.35 (OCH₂CH₂-

Si), 53.27 (CH₃O-4), 65.43 (OCH₂CH₂Si), 72.37 (NCH₂O), 93.54 (C-4a),

106.49 (CH-3-furyl), 107.13 (C-5), 111.69 (CH-4-furyl), 119.55 (CH-

6), 141.15 (CH-5-furyl), 149.16 (C-2-furyl), 155.37 (C-7a), 160.10 (C-

2), 163.37 (C-4).

5-(Thiophen-3-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]meth-

yl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (28d)

Compound 28d was prepared from 13 (420 mg, 1.0 mmol) and thio-

phene-3-boronic acid (192 mg, 1.5 mmol) by GPA′. Flash column

chromatography (30–40% EtOAc/hexanes) gave the product (286 mg,

76%) as a yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.07 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.51 (m, 2 H, OCH₂CH₂Si), 3.98 (s, 3 H, CH₃O-4), 5.37 (s, 2

H, NCH₂O), 6.31 (bs, 2 H, NH₂), 7.37 (s, 1 H, H-6), 7.45 (dd, J_4,5= 5.0 Hz,

J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.50 (dd, J_5,4= 5.0 Hz, J_5,2= 3.0 Hz, 1 H,

H-5-thienyl), 7.77 (dd, J_2,5= 2.9 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.16 (CH₃Si), 17.35 (OCH₂CH₂-

Si), 53.19 (CH₃O-4), 65.39 (OCH₂CH₂Si), 72.27 (NCH₂O), 94.86 (C-4a),

111.76 (C-5), 120.32 (CH-2-thienyl), 121.06 (CH-6), 125.58 (CH-5-

thienyl), 127.71 (CH-4-thienyl), 134.93 (C-3-thienyl), 155.53 (C-7a),

159.79 (C-2), 163.43 (C-4).

MS (ESI): m/z (%) = 361.2 (100) [M + H], 383.2 (40) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅N₄O₃Si: 361.1690; found:

361.1691.

MS (ESI): m/z (%) = 377.2 (100) [M + H], 399.2 (20) [M + Na].

5-(Furan-3-yl)-4-methoxy-7-{[2-(trimethylsilyl)ethoxy]methyl}-

HRMS (ESI): m/z [M + H] calcd for C₁₇H₂₅N₄O₂SSi: 377.1462; found:

7H-pyrrolo[2,3-d]pyrimidin-2-amine (28b)

377.1463.

Compound 28b was prepared from 13 (420 mg, 1.0 mmol) and furan-

3-boronic acid (168 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (30–40% EtOAc/hexanes) gave the product (263 mg, 73%) as a

yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.07 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.49 (m, 2 H, OCH₂CH₂Si), 3.98 (s, 3 H, CH₃O-4), 5.35 (s, 2

H, NCH₂O), 6.30 (bs, 2 H, NH₂), 6.84 (dd, J_4,5= 1.9 Hz, J_4,2= 0.9 Hz, 1 H,

H-4-furyl), 7.31 (s, 1 H, H-6), 7.64 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl),

8.02 (m, 1 H, H-2-furyl).

5-(Benzofuran-2-yl)-4-methoxy-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (28e)

Compound 28e was prepared from 13 (420 mg, 1.0 mmol) and benzo-

furan-2-boronic acid (243 mg, 1.5 mmol) by GPA′. Flash column chro-

matography (40–50% EtOAc/hexanes) gave the product (287 mg, 70%)

as a yellowish oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.07 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.54 (m, 2 H, OCH₂CH₂Si), 4.07 (s, 3 H, CH₃O-4), 5.43 (s, 2

H, NCH₂O), 6.46 (bs, 2 H, NH₂), 7.21 (btd, J_5,4= J_5,6= 7.2 Hz, J_5,7= 1.2 Hz,

1 H, H-5-benzofuryl), 7.24 (bddd, J_6,7= 8.2 Hz, J_6,5= 7.3 Hz, J_6,4= 1.5 Hz,

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.16 (CH₃Si), 17.33 (OCH₂CH₂-

Si), 53.19 (CH₃O-4), 65.34 (OCH₂CH₂Si), 72.21 (NCH₂O), 94.74 (C-4a),

107.21 (C-5), 109.97 (CH-4-furyl), 119.14 (C-3-furyl), 120.36 (CH-6),

N

N. Sabat et al.

Special Topic

Synthesis

1 H, H-6-benzofuryl), 7.31 (d, J_3,7= 1.1 Hz, 1 H, H-3-benzofuryl), 7.50

5-(Furan-2-yl)-4-methoxy-2-methyl-7-{[2-(trimethylsilyl)-

(dm, J_7,6= 8.2 Hz, 1 H, H-7-benzofuryl), 7.60 (s, 1 H, H-6), 7.61 (dm, J_4,5

=

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29a)

7.3 Hz, 1 H, H-4-benzofuryl).

Compound 29a was prepared from 14 (419 mg, 1.0 mmol) and furan-

2-boronic acid (168 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (0–5% EtOAc/hexanes) gave the product (246 mg, 68%) as a col-

orless oil.

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.16 (CH₃Si), 17.37 (OCH₂CH₂Si),

53.47 (CH₃O-4), 65.57 (OCH₂CH₂Si), 72.56 (NCH₂O), 93.74 (C-4a),

102.39 (CH-3-benzofuryl), 106.39 (C-5), 110.55 (CH-7-benzofuryl),

120.78 (CH-4-benzofuryl), 121.96 (CH-6), 123.04 (CH-5-benzofuryl),

123.89 (CH-6-benzofuryl), 129.60 (C-3a-benzofuryl), 151.62 (C-2-

benzofuryl), 153.65 (C-7a-benzofuryl), 155.81 (C-7a), 160.33 (C-2),

163.40 (C-4).

IR (KBr): 3119, 2954, 1743, 1590, 1424, 1249, 1084, 920, 837, 697 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.83 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃-2), 3.53 (m, 2 H, OCH₂CH₂Si), 4.07 (s, 3 H,

CH₃O-4), 5.56 (s, 2 H, NCH₂O), 6.54 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H,

H-4-furyl), 6.90 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.64 (dd,

J_5,4= 1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 7.71 (s, 1 H, H-6).

MS (ESI): m/z (%) = 411.2 (100) [M + H], 433.1 (50) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₁H₂₇N₄O₃Si: 411.1846; found:

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.26 (CH₃Si), 17.27 (OCH₂CH₂Si),

25.69 (CH₃-2), 53.70 (CH₃O-4), 65.76 (OCH₂CH₂Si), 72.67 (NCH₂O),

98.78 (C-4a), 106.71 (C-5), 107.12 (CH-3-furyl), 111.81 (CH-4-furyl),

123.00 (CH-6), 141.60 (CH-5-furyl), 148.46 (C-2-furyl), 153.31 (C-7a),

160.76 (C-2), 162.49 (C-4).

411.1848.

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (28f)

Compound 28f was prepared from 13 (420 mg, 1.0 mmol) and diben-

zo[b,d]furan-4-boronic acid (318 mg, 1.5 mmol) by GPA′. Flash col-

umn chromatography (40–50% EtOAc/hexanes) gave the product (299

mg, 65%) as a colorless oil.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.05 (s, 9 H, (CH₃)₃Si), 0.87 (m, 2

H, CH₂-3′′), 3.60 (m, 2 H, CH₂-2′′), 3.84 (s, 3 H, CH₃O-4), 5.49 (s, 2 H,

CH₂-1′′), 6.38 (bs, 2 H, NH₂-2), 7.40 (m, 1 H, CH-8′), 7.42 (t, J_2′,1′= J_2′,3′

7.7 Hz, 1 H, CH-2′), 7.52 (ddd, J_7′,6′= 8.3 Hz, J_7′,8′= 7.3 Hz, J_7′,9′= 1.4 Hz, 1

H, CH-7′), 7.59 (s, 1 H, CH-6), 7.67 (dt, J_6′,7′= 8.3 Hz, J_6′,8′= J_6′,9′= 0.8 Hz, 1

H, CH-6′), 7.80 (dd, J_3′,2′= 7.7 Hz, J_3′,1′= 1.3 Hz, 1 H, CH-3′), 8.01 (dd, J_1′,2′

7.7 Hz, J_1′,3′=1.3 Hz, 1 H, CH-1′), 8.16 (ddd, J_9′,8′= 7.7 Hz, J_9′,7′= 1.3 Hz,

J_9′,6′= 0.8 Hz, 1 H, CH-9′).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.12 ((CH₃)₃Si), 17.46 (CH₂-3′′),

53.20 (CH₃O-4), 65.59 (CH₂-2′′), 72.53 (CH₂-1′′), 95.81 (C-4a), 110.02

(C-5), 111.75 (CH-6′), 118.92 (CH-1′), 119.54 (C-4′), 121.36 (CH-9′),

123.11 (CH-2′/8′), 123.24 (CH-2′/8′), 123.44 (CH-6), 123.72 (C-

9a′/9b′), 124.07 (C-9a′/9b′), 127.66 (CH-7′), 128.55 (CH-3′), 153.12 (C-

4a′), 155.46 (C-5a′/7a), 155.56 (C-5a′/7a), 159.97 (C-2), 163.63 (C-4).

MS (ESI): m/z (%) = 360.2 (100) [M + H], 382.2 (40) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₈H₂₆N₃O₃Si: 360.1738; found:

360.1738.

5-(Furan-3-yl)-4-methoxy-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29b)

=

Compound 29b was prepared from 14 (419 mg, 1.0 mmol) and furan-

3-boronic acid (168 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (0–5% EtOAc/hexanes) gave the product (274 mg, 76%) as a yel-

lowish oil.

=

IR (KBr): 3115, 2951, 1756, 1591, 1462, 1253, 1097, 932, 851, 700 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃-2), 3.52 (m, 2 H, OCH₂CH₂Si), 4.06 (s, 3 H,

CH₃O-4), 5.53 (s, 2 H, NCH₂O), 6.91 (dd, J_4,5= 1.9 Hz, J_4,2= 0.9 Hz, 1 H,

H-4-furyl), 7.68 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 7.73 (s, 1 H, H-6),

8.09 (m, 1 H, H-2-furyl).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.23 (CH₃Si), 17.27 (OCH₂CH₂Si),

25.72 (CH₃-2), 53.65 (CH₃O-4), 65.70 (OCH₂CH₂Si), 72.51 (NCH₂O),

99.92 (C-4a), 106.90 (C-5), 110.10 (CH-4-furyl), 118.63 (C-3-furyl),

123.90 (CH-6), 139.93 (CH-2-furyl), 143.48 (CH-5-furyl), 153.54 (C-

7a), 160.42 (C-2), 162.52 (C-4).

MS (ESI): m/z (%) = 461.2 (65) [M + H], 483.2 (100) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₂₅H₂₈N₄O₃NaSi: 483.1822; found:

483.1821.

4-Methoxy-5-phenyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-

pyrrolo[2,3-d]pyrimidin-2-amine (28g)

MS (ESI): m/z (%) = 360.2 (100) [M + H], 382.2 (90) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₈H₂₆N₃O₃Si: 360.1738; found:

360.1739.

Compound 28g was prepared from 13 (420 mg, 1.0 mmol) and phen-

ylboronic acid (183 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (40–50% EtOAc/hexanes) gave the product (252 mg, 68%) as a

yellowish oil.

4-Methoxy-2-methyl-5-(thiophen-2-yl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29c)

¹H NMR (500 MHz, DMSO-d₆): δ = –0.07 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 3.53 (m, 2 H, OCH₂CH₂Si), 3.90 (s, 3 H, CH₃O-4), 5.39 (s, 2

H, NCH₂O), 6.31 (s, 2 H, NH₂), 7.22 (s, 1 H, H-6), 7.23 (m, 1 H, H-p-Ph),

7.36 (m, 2 H, H-m-Ph), 7.60 (m, 2 H, H-o-Ph).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.16 (CH₃Si), 17.37 (OCH₂CH₂Si),

53.12 (CH₃O-4), 65.45 (OCH₂CH₂Si), 72.35 (NCH₂O), 95.12 (C-4a),

116.68 (C-5), 121.20 (CH-6), 126.12 (CH-p-Ph), 128.11 and 128.25

(CH-m,o-Ph), 134.72 (C-i-Ph), 155.69 (C-7a), 159.77 (C-2), 163.55 (C-

4).

Compound 29c was prepared from 14 (419 mg, 1.0 mmol) and thio-

phen-2-boronic acid (192 mg, 1.5 mmol) by GPA′. Flash column chro-

matography (0–5% EtOAc/hexanes) gave the product (301 mg, 80%) as

a pinkish oil.

IR (KBr): 3107, 2950, 1747, 1556, 1414, 1277, 1086, 978, 838, 697 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.57 (s, 3 H, CH₃-2), 3.54 (m, 2 H, OCH₂CH₂Si), 4.01 (s, 3 H,

CH₃O-4), 5.55 (s, 2 H, NCH₂O), 7.08 (dd, J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1 H,

H-4-thienyl), 7.41 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.46

(dd, J_3,4= 3.6 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl), 7.70 (s, 1 H, H-6).

MS (ESI): m/z (%) = 371.2 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₉H₂₇N₄O₂Si: 371.1897; found:

371.1899.

O

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.27 (CH₃Si), 17.25 (OCH₂CH₂Si),

25.68 (CH₃-2), 53.54 (CH₃O-4), 65.77 (OCH₂CH₂Si), 72.54 (NCH₂O),

99.80 (C-4a), 109.52 (C-5), 124.30 (CH-6, CH-5-thienyl), 125.65 (CH-

3-thienyl), 127.86 (CH-4-thienyl), 135.90 (C-2-thienyl), 153.34 (C-7a),

160.55 (C-2), 162.53 (C-4).

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-2-methyl-7-{[2-(trimeth-

ylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29f)

Compound 29f was prepared from 14 (419 mg, 1.0 mmol) and diben-

zo[b,d]furan-4-boronic acid (318 mg, 1.5 mmol) by GPA′. Flash col-

umn chromatography (5–10% EtOAc/hexanes) gave the product (327

mg, 71%) as a colorless oil.

MS (ESI): m/z (%) = 376.1 (100) [M + H], 398.1 (40) [M + Na].

IR (KBr): 3055, 2951, 1591, 1450, 1347, 1207, 1090, 923, 757, 697 cm^–1

.

HRMS (ESI): m/z [M + H] calcd for C₁₈H₂₆N₃O₂SSi: 376.1509; found:

¹H NMR (500 MHz, DMSO-d₆): δ = –0.06 (s, 9 H, CH₃Si), 0.89 (m, 2 H,

OCH₂CH₂Si), 2.61 (s, 3 H, CH₃-2), 3.63 (m, 2 H, OCH₂CH₂Si), 3.91 (s, 3 H,

CH₃O-4), 5.67 (s, 2 H, NCH₂O), 7.41 (td, J_8,9= J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1

H, H-8-C₁₂H₇O), 7.46 (t, J_2,1= J_2,3= 7.7 Hz, 1 H, H-2-C₁₂H₇O), 7.52 (ddd,

376.1510.

4-Methoxy-2-methyl-5-(thiophen-3-yl)-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29d)

J_7,6= 8.2 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₂H₇O), 7.67 (dt, J_6,7

8.2 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₂H₇O), 7.81 (dd, J_3,2= 7.6 Hz, J_3,1

1.3 Hz, 1 H, H-3-C₁₂H₇O), 7.97 (s, 1 H, H-6), 8.07 (dd, J_1,2= 7.7 Hz, J_1,3

1.3 Hz, 1 H, H-1-C₁₂H₇O), 8.18 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7

Hz, 1 H, H-9-C₁₂H₇O).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.22 (CH₃Si), 17.36 (OCH₂CH₂-

Si), 25.74 (CH₃-2), 53.55 (CH₃O-4), 65.92 (OCH₂CH₂Si), 72.79 (NCH₂O),

101.03 (C-4a), 109.51 (C-5), 111.75 (CH-6-C₁₂H₇O), 118.80 (C-4-

=

Compound 29d was prepared from 14 (419 mg, 1.0 mmol) and thio-

phen-3-boronic acid (192 mg, 1.5 mmol) by GPA′. Flash column chro-

matography (0–5% EtOAc/hexanes) gave the product (331 mg, 88%) as

a greenish oil.

IR (KBr): 3130, 2951, 1599, 1556, 1344, 1209, 1089, 926, 776, 697 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.56 (s, 3 H, CH₃-2), 3.53 (m, 2 H, OCH₂CH₂Si), 4.05 (s, 3 H,

CH₃O-4), 5.54 (s, 2 H, NCH₂O), 7.51 (dd, J_4,5= 5.0 Hz, J_4,2= 1.3 Hz, 1 H,

H-4-thienyl), 7.54 (dd, J_5,4= 5.0 Hz, J_5,2= 2.9 Hz, 1 H, H-5-thienyl), 7.77

(s, 1 H, H-6), 7.84 (dd, J_2,5= 2.9 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.27 (CH₃Si), 17.25 (OCH₂CH₂-

Si), 25.68 (CH₃-2), 53.54 (CH₃O-4), 65.77 (OCH₂CH₂Si), 72.54 (NCH₂O),

99.80 (C-4a), 109.52 (C-5), 124.30 (CH-6, CH-5-thienyl), 125.65 (CH-

3-thienyl), 127.86 (CH-4-thienyl), 135.90 (C-2-thienyl), 153.34 (C-7a),

160.55 (C-2), 162.53 (C-4).

C

₁₂H₇O), 119.40 (CH-1-C₁₂H₇O), 121.38 (CH-9-C₁₂H₇O), 123.13 (CH-2-

₁₂H₇O), 123.26 (CH-8-C₁₂H₇O), 123.79 (C-9b-C₁₂H₇O), 123.97 (C-9a-

₁₂H₇O), 126.79 (CH-6), 127.70 (CH-7-C₁₂H₇O), 128.79 (CH-3-C₁₂H₇O),

153.18 (C-4a-C₁₂H₇O), 153.37 (C-7a), 155.56 (C-5a-C₁₂H₇O), 160.40

(C-2), 162.70 (C-4).

MS (ESI): m/z (%) = 460.3 (100) [M + H], 483.2 (30) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₆H₃₀N₃O₃Si: 460.2051; found:

460.2052.

MS (ESI): m/z (%) = 376.2 (100) [M + H], 398.1 (40) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₈H₂₆N₃O₂SSi: 376.1509; found:

376.1510.

4-Methoxy-2-methyl-5-phenyl-7-{[2-(trimethylsi-

lyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29g)

Compound 29g was prepared from 14 (419 mg, 1.0 mmol) and phen-

ylboronic acid (183 mg, 1.5 mmol) by GPA′. Flash column chromatog-

raphy (0–5% EtOAc/hexanes) gave the product (237 mg, 64%) as a yel-

lowish oil.

5-(Benzofuran-2-yl)-4-methoxy-2-methyl-7-{[2-(trimethylsilyl)-

ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine (29e)

Compound 29e was prepared from 14 (419 mg, 1.0 mmol) and benzo-

furan-2-boronic acid (243 mg, 1.5 mmol) by GPA′. Flash column chro-

matography (5–10% EtOAc/hexanes) gave the product (312 mg, 76%)

as a colorless oil.

IR (KBr): 2951, 2895, 1590, 1347, 1201, 1090, 919, 838, 763, 697 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.10 (s, 9 H, CH₃Si), 0.84 (m, 2 H,

OCH₂CH₂Si), 2.58 (s, 3 H, CH₃-2), 3.56 (m, 2 H, OCH₂CH₂Si), 3.98 (s, 3 H,

CH₃O-4), 5.57 (s, 2 H, NCH₂O), 7.26 (m, 1 H, H-p-Ph), 7.39 (m, 2 H, H-

m-Ph), 7.63 (s, 1 H, H-6), 7.64 (m, 2 H, H-o-Ph).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.29 (CH₃Si), 17.28 (OCH₂CH₂Si),

25.66 (CH₃-2), 53.47 (CH₃O-4), 65.77 (OCH₂CH₂Si), 72.59 (NCH₂O),

100.23 (C-4a), 116.20 (C-5), 124.73 (CH-6), 126.44 (CH-p-Ph), 128.31

(CH-m-Ph), 128.43 (CH-o-Ph), 134.04 (C-i-Ph), 153.63 (C-7a), 160.12

(C-2), 162.61 (C-4).

IR (KBr): 3059, 2950, 1593, 1463, 1347, 1249, 1093, 862, 750, 696 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = –0.09 (s, 9 H, CH₃Si), 0.85 (m, 2 H,

OCH₂CH₂Si), 2.59 (s, 3 H, CH₃-2), 3.57 (m, 2 H, OCH₂CH₂Si), 4.15 (s, 3 H,

CH₃O-4), 5.61 (s, 2 H, NCH₂O), 7.23 (btd, J_5,6= J_5,4= 7.4 Hz, J_5,7= 1.3 Hz,

1 H, H-5-benzofuryl), 7.27 (ddd, J_6,7= 7.9 Hz, J_6,5= 7.3 Hz, J_6,4= 1.5 Hz,

1 H, H-6-benzofuryl), 7.39 (d, J_3,7= 1.0 Hz, 1 H, H-3-benzofuryl), 7.54

(dq, J_7,6= 7.9 Hz, J_7,5= J_7,4= J_7,3= 1.0 Hz, 1 H, H-7-benzofuryl), 7.64

(dm, J_4,5= 7.4 Hz, 1 H, H-4-benzofuryl), 8.00 (s, 1 H, H-6).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = –1.23 (CH₃Si), 17.30 (OCH₂CH₂-

Si), 25.74 (CH₃-2), 53.96 (CH₃O-4), 65.92 (OCH₂CH₂Si), 72.90 (NCH₂O),

99.15 (C-4a), 103.08 (CH-3-benzofuryl), 105.95 (C-5), 110.68 (CH-7-

benzofuryl), 121.00 (CH-4-benzofuryl), 123.18 (CH-5-benzofuryl),

124.19 (CH-6-benzofuryl), 125.32 (CH-6), 129.44 (C-3a-benzofuryl),

150.87 (C-2-benzofuryl), 153.73 and 153.75 (C-7a, C-7a-benzofuryl),

161.21 (C-2), 162.55 (C-4).

MS (ESI): m/z (%) = 370.2 (100) [M + H], 392.2 (60) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₀H₂₈N₃O₂Si: 370.1945; found:

370.1947.

4-Amino-5-(furan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (30a)

Compound 30a was prepared from 23a (220 mg, 0.66 mmol) by GPC.

Column chromatography (0.5% MeOH/CHCl₃) then recrystallization

(MeOH) gave the product (52 mg, 39%) as an orange solid; mp 271–

272 °C.

MS (ESI): m/z (%) = 410.2 (100) [M + H], 432.2 (90) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₂₂H₂₈N₃O₃Si: 410.1894; found:

410.1898.

IR (KBr): 1643, 1574, 1320, 1158, 870, 790 cm^–1

.

¹H NMR (499.8 MHz, DMSO-d₆): δ = 6.58 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz,

1 H, H-4-furyl), 6.64 (dd, J_3,4= 3.3 Hz, J_3,5= 0.8 Hz, 1 H, H-3-furyl), 6.79

(bs, 2 H, NH₂), 7.56 (s, 1 H, H-6), 7.75 (dd, J_5,4= 1.9 Hz, J_5,3= 0.8 Hz, 1 H,

H-5-furyl), 8.09 (s, 1 H, H-2), 11.92 (bs, 1 H, NH).

P

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 98.85 (C-4a), 104.74 (CH-3-fu-

ryl), 108.32 (C-5), 105.75 (CH-4-furyl), 120.18 (CH-6), 141.69 (CH-5-

furyl), 149.52 (C-2-furyl), 151.66 (C-7a), 152.29 (CH-2), 157.34 (C-4).

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄S: 217.0542; found:

217.0543.

4-Amino-5-(benzofuran-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (30e)

MS (ESI): m/z (%) = 201.1 (100) [M + H], 223.0 (5) [M + Na].

Compound 30e was prepared from 23e (294 mg, 0.77 mmol) by GPC.

Recrystallization (MeOH) gave the product (156 mg, 81%) as a white

solid; mp 328 °C.

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉ON₄: 201.0771; found:

201.0771.

IR (KBr): 1656, 1577, 1464, 1325, 809, 750 cm^–1

.

4-Amino-5-(furan-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (30b)

Compound 30b was prepared from 23b (220 mg, 0.66 mmol) by GPC.

Column chromatography (0.5% MeOH/CHCl₃) then recrystallization

(MeOH) gave the product (119 mg, 66%) as a white solid; mp 158 °C.

¹H NMR (499.8 MHz, DMSO-d₆): δ = 6.93 (bs, 2 H, NH₂), 7.11 (d, J_3,7

0.9 Hz, 1 H, H-3-benzofuryl), 7.25 (ddd, J_6,7= 8.9 Hz, J_6,5= 7.3 Hz, J_6,4

1.8 Hz, 1 H, H-6-benzofuryl), 7.27 (ddd, J_5,4= 9.5 Hz, J_5,6= 7.3 Hz, J_5,7

=

2.1 Hz, 1 H, H-5-benzofuryl), 7.61 (m, 1 H, H-4-benzofuryl), 7.65 (m, 1

H, H-7-benzofuryl), 7.84 (s, 1 H, H-6), 8.16 (s, 1 H, H-2), 12.19 (bs, 1 H,

NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 98.98 (C-4a), 100.99 (CH-3-ben-

zofuryl), 105.09 (C-5), 111.16 (CH-7-benzofuryl), 120.62 (CH-4-ben-

zofuryl), 122.67 (CH-6), 123.60, 123.75 (CH-5,6-benzofuryl), 129.17

(C-3a-benzofuryl), 151.99, 152.03 (C-7a, C-2-benzofuryl), 152.41

(CH-2), 153.84 (C-7a-benzofuryl), 157.30 (C-4).

IR (KBr): 1643, 1576, 1325, 1158, 873, 792 cm^–1

¹H NMR (499.8 MHz, DMSO-d₆): δ = 6.13 (bs, 2 H, NH₂), 6.70 (dd, J_4,5

1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.20 (d, J_6,NH= 1.8 Hz, 1 H, H-6),

7.78 (dd, J_5,4= 1.8 Hz, J_5,2= 1.6 Hz, 1 H, H-5-furyl), 7.80 (dd, J_2,5= 1.6

Hz, J_2,4= 0.9 Hz, 1 H, H-2-furyl), 8.09 (s, 1 H, H-2), 11.73 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 100.50 (C-4a), 105.64 (C-5),

111.84 (CH-4-furyl), 119.43 (C-3-furyl), 120.41 (CH-6), 139.47 (CH-2-

furyl), 144.20 (CH-5-furyl), 151.52 (C-7a), 151.97 (CH-2), 157.54 (C-

4).

.

=

MS (ESI): m/z (%) = 251.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₄H₁₁ON₄: 251.0927; found:

251.0928.

MS (ESI): m/z (%) = 201.1 (100) [M + H], 223.0 (5) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉ON₄: 201.0771; found:

201.0771.

4-Amino-5-(dibenzo[b,d]furan-4-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (30f)

4-Amino-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (30c)

Compound 30f was prepared from 23f (396 mg, 0.92 mmol) by GPC.

Recrystallization (MeOH) gave the product (222 mg, 80%) as a yellow-

ish solid; mp 313 °C.

Compound 30c was prepared from 23c (203 mg, 0.59 mmol) by GPC.

Recrystallization (MeOH) gave the product (94 mg, 73%) as a white

solid; mp 279 °C.

IR (KBr): 1639, 1570, 1474, 1456, 1187, 801, 755 cm^–1

¹H NMR (499.8 MHz, DMSO-d₆): δ = 5.95 (bs, 2 H, NH₂), 7.42 (ddd, J_8,9

.

IR (KBr): 1654, 1601, 1576, 1468, 1328, 806, 710 cm^–1

¹H NMR (499.8 MHz, DMSO-d₆): δ = 6.21 (bs, 2 H, NH₂), 7.12 (dd, J_3,4

.

=

8.2 Hz, J_8,9= 7.7 Hz, J_8,6= 0.8 Hz, 1 H, H-8-dibenzofuryl), 7.49 (s, 1 H,

H-6), 7.50–7.55 (m, 3 H, H-2,3,7-dibenzofuryl), 7.70 (d, J_6,7= 8.2 Hz, 1

H, H-6-dibenzofuryl), 8.13 (dd, J_1,2= 7.0 Hz, J_1,2= 2.0 Hz, 1 H, H-1-

dibenzofuryl), 8.16 (s, 1 H, H-2), 8.19 (d, J_9,8= 7.7 Hz, 1 H, H-9-diben-

zofuryl), 11.98 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 100.95 (C-4a), 108.96 (C-5, C-4-

dibenzofuryl), 112.03 (CH-6-dibenzofuryl), 119.86 (CH-1-dibenzofu-

ryl), 121.50 (CH-9-dibenzofuryl), 122.20 (CH-6), 123.37 (CH-8-diben-

zofuryl), 123.77 (CH-2-dibenzofuryl), 124.07 (C-9a-dibenzofuryl),

124.29 (C-9b-dibenzofuryl), 127.83 (CH-7-dibenzofuryl), 128.60 (CH-

3-dibenzofuryl), 151.62 (C-7a), 152.06 (CH-2), 153.44 (C-4a-dibenzo-

furyl), 155.70 (C-5a-dibenzofuryl), 157.55 (C-4).

3.4 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl), 7.16 (dd, J_4,5= 5.2 Hz, J_4,3= 3.4

Hz, 1 H, H-4-thienyl), 7.30 (s, 1 H, H-6), 7.53 (dd, J_5,4= 5.2 Hz, J_5,3= 1.2

Hz, 1 H, H-5-thienyl), 8.12 (s, 1 H, H-2), 11.91 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 100.19 (C-4a), 107.90 (C-5),

121.65 (CH-6), 125.60 (CH-5-thienyl), 126.11 (CH-3-thienyl), 128.39

(CH-4-thienyl), 136.65 (C-2-thienyl), 151.43 (C-7a), 152.24 (CH-2),

157.34 (C-4).

MS (ESI): m/z (%) = 217.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄S: 217.05424; found:

217.05425.

MS (ESI): m/z (%) = 301.1 (100) [M + H], 323.1 (10) [M + Na].

4-Amino-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (30d)

Compound 30d was prepared from 23d (305 mg, 0.88 mmol) by GPC.

Recrystallization (H₂O) gave the product (182 mg, 96%) as a white sol-

id; mp 283 °C.

HRMS (ESI): m/z [M + H] calcd for C₁₈H₁₃ON₄: 301.1084; found:

301.1084.

IR (KBr): 1647, 1575, 1553, 1471, 854, 810, 783, 718 cm^–1

.

4-Amino-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (30g)

¹H NMR (499.8 MHz, DMSO-d₆): δ = 6.10 (bs, 2 H, NH₂), 7.26 (s, 1 H,

H-6), 7.275 (dd, J_4,5= 4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.47 (dd,

Compound 30g was prepared from 23g (320 mg, 0.94 mmol) by GPC.

Recrystallization (MeOH) gave the product (178 mg, 90%) as a white

solid; mp 258 °C.

J_2,5= 2.9 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.68 (dd, J_5,4= 4.9 Hz, J_5,2

=

IR (KBr): 1652, 1580, 1529, 1459, 1326, 964, 764, 756 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 6.01 (bs, 2 H, NH₂), 7.25 (d, J_6,NH

1.8 Hz, 1 H, H-6), 7.34 (m, 1 H, H-p-Ph), 7.44–7.49 (m, 2 × 2 H, H-m,o-

Ph), 8.12 (s, 1 H, H-2), 11.82 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 99.98 (C-4a), 115.92 (C-5),

120.59 (CH-6), 126.72 (CH-p-Ph), 128.65 (CH-o-Ph), 129.12 (CH-m-

Ph), 135.39 (C-i-Ph), 151.68 (C-7a), 151.91 (CH-2), 157.36 (C-4).

.

2.9 Hz, 1 H, H-5-thienyl), 8.11 (s, 1 H, H-2), 11.77 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 100.28 (C-4a), 110.51 (C-5),

120.55 (CH-6), 121.56 (CH-2-thienyl), 127.32 (CH-5-thienyl), 128.83

(CH-4-thienyl), 135.72 (C-3-thienyl), 151.38 (C-7a), 151.96 (CH-2),

157.47 (C-4).

=

MS (ESI): m/z (%) = 217.1 (100) [M + H].

Q

N. Sabat et al.

Special Topic

Synthesis

MS (ESI): m/z (%) = 211.1 (100) [M + H].

4-Amino-2-methyl-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (31d)

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₁N₄: 211.0978; found:

Compound 31d was prepared from 24d (350 mg, 0.97 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (161 mg, 72%) as a

white solid; mp 336 °C.

IR (KBr): 1653, 1609, 1573, 1397, 1327, 818, 784 cm^–1

.

211.0978.

4-Amino-5-(furan-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine

(31a)

¹H NMR (500 MHz, DMSO-d₆): δ = 2.38 (s, 3 H, CH₃-2), 6.04 (bs, 2 H,

NH₂), 7.17 (d, J_6,NH= 2.3 Hz, 1 H, H-6), 7.26 (dd, J_4,5= 4.9 Hz, J_4,2= 1.3

Hz, 1 H, H-4-thienyl), 7.44 (dd, J_2,5= 2.9 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thie-

nyl), 7.67 (dd, J_5,4= 4.9 Hz, J_5,2= 2.9 Hz, 1 H, H-5-thienyl), 11.57 (bs, 1

H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.34 (CH₃-2), 98.05 (C-4a),

110.50 (C-5), 119.89 (CH-6), 121.29 (CH-2-thienyl), 127.29 (CH-5-

thienyl), 128.73 (CH-4-thienyl), 135.87 (C-3-thienyl), 152.33 (C-7a),

157.11 (C-4), 159.91 (C-2).

Compound 31a was prepared from 24a (255 mg, 0.74 mmol) by GPD.

Recrystallization (MeOH/H₂O) gave the product (94 mg, 59%) as a

brownish solid; mp >200 °C (dec).

IR (KBr): 1652, 1566, 1526, 1493, 1014, 815, 791, 717 cm^–1

.

¹H NMR (500 MHz, CDCl₃): δ = 2.37 (s, 3 H, CH₃-2), 5.67 (dd, J_4,3= 3.3

Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 6.61 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H,

H-3-furyl), 6.72 (bs, 2 H, NH₂), 7.46 (s, 1 H, H-6), 7.73 (dd, J_5,4= 1.9 Hz,

J_5,3= 0.9 Hz, 1 H, H-5-furyl), 11.70 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.40 (CH₃-2), 96.64 (C-4a),

104.41 (CH-3-furyl), 105.65 (C-5), 112.03 (CH-4-furyl), 119.42 (CH-

6), 141.51 (CH-5-furyl), 149.76 (C-2-furyl), 152.70 (C-7a), 157.15 (C-

4), 160.52 (C-2).

MS (ESI): m/z (%) = 231.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄S: 231.0699; found:

231.0699.

MS (ESI): m/z (%) = 215.1 (100) [M + H].

4-Amino-5-(benzofuran-2-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimi-

dine (31e)

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁ON₄: 215.0927; found:

215.0927.

Compound 31e was prepared from 24e (343 mg, 0.87 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (225 mg, 98%) as a

white solid; mp >200 °C (dec).

4-Amino-5-(furan-3-yl)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine

(31b)

IR (KBr): 1645, 1595, 1567, 1455, 1320, 1256, 817, 791, 745 cm^–1

.

Compound 31b was prepared from 24b (290 mg, 0.84 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (149 mg, 83%) as a

brownish solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 2.40 (s, 3 H, CH₃-2), 6.84 (bs, 2 H,

NH₂), 7.08 (d, J_3,7= 1.0 Hz, 1 H, H-3-benzofuryl), 7.22–7.29 (m, 2 H, H-

5,6-benzofuryl), 7.57–7.67 (m, 2 H, H-4,7-benzofuryl), 7.75 (s, 1 H, H-

6), 11.96 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.41 (CH₃-2), 96.77 (C-4a),

100.64 (CH-3-benzofuryl), 104.93 (C-5), 111.10 (CH-7-benzofuryl),

120.53 (CH-4-benzofuryl), 121.93 (CH-6), 123.56 and 123.65 (CH-5,6-

benzofuryl), 129.20 (C-3a-benzofuryl), 152.30 (C-2-benzofuryl),

153.05 (C-7a), 153.77 (C-7a-benzofuryl), 157.16 (C-4), 160.81 (C-2).

IR (KBr): 1645, 1572, 1460, 1310, 1157, 1033, 872, 784 cm^–1

.

¹H NMR (500 MHz, CDCl₃): δ = 2.37 (s, 3 H, CH₃-2), 6.08 (bs, 2 H, NH₂),

6.68 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.12 (d, J_6,NH= 1.8

Hz, 1 H, H-6), 7.77 (t, J_5,2= J_5,4= 1.7 Hz, 1 H, H-5-furyl), 7.78 (dd, J_2,5

1.6 Hz, J_2,4= 0.9 Hz, 1 H, H-2-furyl), 11.54 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.37 (CH₃-2), 98.26 (C-4a),

105.58 (C-5), 111.74 (CH-4-furyl), 119.57 (C-3-furyl), 119.71 (CH-6),

139.29 (CH-2-furyl), 144.15 (CH-5-furyl), 152.50 (C-7a), 157.23 (C-4),

159.97 (C-2).

=

MS (ESI): m/z (%) = 265.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₅H₁₃ON₄: 265.1084; found:

265.1084.

MS (ESI): m/z (%) = 215.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁ON₄: 215.0927; found:

215.0927.

4-Amino-5-(dibenzo[b,d]furan-4-yl)-2-methyl-7H-pyrrolo[2,3-

d]pyrimidine (31f)

Compound 31f was prepared from 24f (356 mg, 0.8 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (214 mg, 85%) as a

white solid; mp 160–161 °C.

4-Amino-2-methyl-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (31c)

Compound 31c was prepared from 24c (334 mg, 0.93 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (195 mg, 91%) as a

white solid; mp 137 °C.

IR (KBr): 1640, 1569, 1451, 1191, 841, 753 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.42 (s, 3 H, CH₃-2), 5.88 (bs, 2 H,

NH₂), 7.40 (d, J_6,NH= 2.1 Hz, 1 H, H-6), 7.42 (btd, J_8,9= J_8,7= 7.5 Hz, J_8,6

1.0 Hz, 1 H, H-8-C₁₂H₇O), 7.47–7.52 (m, 2 H, H-2,3-C₁₂H₇O), 7.52 (ddd,

J_7,6= 8.3 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₂H₇O), 7.70 (dt, J_6,7

.

IR (KBr): 1651, 1612, 1574, 1326, 1300, 844, 818, 791, 775 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.38 (s, 3 H, CH₃-2), 6.15 (bs, 2 H,

.

=

NH₂), 7.10 (dd, J_3,4= 3.5 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl), 7.14 (dd, J_4,5

5.2 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.21 (s, 1 H, H-6), 7.50 (dd, J_5,4

5.2 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 11.71 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.42 (CH₃-2), 97.99 (C-4a),

107.86 (C-5), 120.89 (CH-6), 125.36 (CH-5-thienyl), 125.81 (CH-3-

thienyl), 128.36 (CH-4-thienyl), 136.92 (C-2-thienyl), 152.45 (C-7a),

157.10 (C-4), 160.43 (C-2).

=

8.2 Hz, J_6,8= J_6,9= 0.8 Hz, 1 H, H-6-C₁₂H₇O), 8.11 (m, 1 H, H-1-C₁₂H₇O),

8.19 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-C₁₂H₇O),

11.79 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.46 (CH₃-2), 98.74 (C-4a),

108.87 (C-5), 112.01 (CH-6-C₁₂H₇O), 119.71 (CH-1-C₁₂H₇O), 120.07

(C-4-C₁₂H₇O), 121.49 and 121.51 (CH-6, CH-9-C₁₂H₇O), 123.36 (CH-8-

C

₁₂H₇O), 123.77 (CH-2-C₁₂H₇O), 124.08 and 124.27 (C-9a,9b-C₁₂H₇O),

MS (ESI): m/z (%) = 231.1 (100) [M + H].

127.82 (CH-7-C₁₂H₇O), 128.43 (CH-3-C₁₂H₇O), 152.65 (C-7a), 153.36

(C-4a-C₁₂H₇O), 155.68 (C-5a-C₁₂H₇O), 157.33 (C-4), 160.22 (C-2).

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄S: 231.0699; found:

231.0699.

R

N. Sabat et al.

Special Topic

Synthesis

MS (ESI): m/z (%) = 315.1 (100) [M + H].

¹H NMR (500 MHz, DMSO-d₆): δ = 4.06 (s, 3 H, CH₃O), 7.07 (dd, J_4,5

=

5.1 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.40 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2

Hz, 1 H, H-3-thienyl), 7.44 (dd, J_3,4= 3.5 Hz, J_3,5= 1.2 Hz, 1 H, H-3-thie-

nyl), 7.63 (d, J_6,NH= 2.6 Hz, 1 H, H-6), 8.40 (s, 1 H, H-2), 12.32 (bs, 1 H,

NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.57 (CH₃O), 101.75 (C-4a),

109.17 (C-5), 122.26 (CH-6), 124.13 (CH-5-thienyl), 125.35 (CH-3-

thienyl), 127.76 (CH-4-thienyl), 136.45 (C-2-thienyl), 151.09 (CH-2),

153.08 (C-7a), 162.69 (C-4).

HRMS (ESI): m/z [M + H] calcd for C₁₉H₁₅ON₄: 315.1240; found:

315.1241.

4-Amino-2-methyl-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (31g)

Compound 31g was prepared from 24g (335 mg, 0.95 mmol) by GPC.

Recrystallization (MeOH/H₂O) gave the product (171 mg, 80%) as a

white solid; mp 322 °C.

IR (KBr): 1652, 1597, 1563, 1531, 1484, 1318, 814, 754 cm^–1

.

MS (ESI): m/z (%) = 230.0 (100) [M – H].

¹H NMR (500 MHz, DMSO-d₆): δ = 2.39 (s, 3 H, CH₃-2), 5.93 (bs, 2 H,

NH₂), 7.15 (d, J_6,NH= 1.4 Hz, 1 H, H-6), 7.32 (m, 1 H, H-p-Ph), 7.42–7.48

(m, 2 × 2 H, H-m,o-Ph), 11.60 (bs, 1 H, NH).

HRMS (ESI): m/z [M – H] calcd for C₁₁H₈ON₃S: 230.03936; found:

230.03936.

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.47 (CH₃-2), 97.81 (C-4a),

115.83 (C-5), 119.85 (CH-6), 126.62 (CH-p-Ph), 128.51 and 129.12

(CH-o,m-Ph), 135.61 (C-i-Ph), 152.78 (C-7a), 157.23 (C-4), 160.18 (C-

2).

4-Methoxy-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (32d)

Compound 32d was prepared from 25d (400 mg, 1.16 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (217 mg, 85%) as a white solid; mp 250–251 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 4.07 (s, 3 H, CH₃O), 7.45 (dd, J_5,4

5.0 Hz, J_5,2= 2.7 Hz, 1 H, H-5-thienyl), 7.55 (dd, J_4,5= 5.0 Hz, J_4,2= 1.5

Hz, 1 H, H-4-thienyl), 7.72 (s, 1 H, H-6), 7.82 (dd, J_2,5= 2.7 Hz, J_2,4= 1.5

Hz, 1 H, H-2-thienyl), 8.39 (s, 1 H, H-2), 12.22 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.65 (CH₃O), 101.94 (C-4a),

111.03 (C-5), 120.71 (CH-2-thienyl), 122.37 (CH-6), 125.70 (CH-5-

thienyl), 128.14 (CH-4-thienyl), 134.82 (C-3-thienyl), 150.82 (CH-2),

153.19 (C-7a), 162.70 (C-4).

MS (ESI): m/z (%) = 225.1 (100) [M + H].

=

HRMS (ESI): m/z [M + H] calcd for C₁₃H₁₃N₄: 225.1135; found:

225.1135.

5-(Furan-2-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (32a)

Compound 32a was prepared from 25a (270 mg, 0.78 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (87 mg, 52%) as a brownish solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 4.09 (s, 3 H, CH₃O), 6.53 (dd, J_4,3

=

MS (EI): m/z (%) = 231.0 (100) [M], 232.0 (10) [M + H].

3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 6.88 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz,

1 H, H-3-furyl), 7.62 (dd, J_5,4= 1.8 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 7.63

(d, J_6,NH= 2.6 Hz, 1 H, H-6), 8.40 (s, 1 H, H-2), 12.32 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 54.18 (CH₃O), 101.08 (C-4a),

106.90 (C-5), 107.03 (CH-3-furyl), 112.20 (CH-4-furyl), 121.22 (CH-

6), 141.73 (CH-5-furyl), 149.13 (C-2-furyl), 151.65 (CH-2), 153.26 (C-

7a), 163.07 (C-4).

HRMS (EI): m/z [M] calcd for C₁₁H₉N₃OS: 231.0466; found: 231.0467.

5-(Benzofuran-2-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine

(32e)

Compound 32e was prepared from 25e (350 mg, 0.89 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (228 mg, 98%) as a yellowish solid; mp 276–277 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 4.16 (s, 3 H, CH₃O), 7.22 (td, J_5,6= J_5,4

7.3 Hz, J_5,7= 1.2 Hz, 1 H, H-5-benzofuryl), 7.25 (bddd, J_6,7= 8.0 Hz, J_6,5

7.3 Hz, J_6,4= 1.5 Hz, 1 H, H-6-benzofuryl), 7.37 (d, J_3,7= 1.1 Hz, 1 H, H-

3-benzofuryl), 7.53 (bdq, J_7,6= 8.0 Hz, J_7,5= J_7,4= J_7,3= 1.0 Hz, 1 H, H-7-

benzofuryl), 7.63 (ddd, J_4,5= 7.3 Hz, J_4,6= 1.5 Hz, J_4,7= 0.7 Hz, 1 H, H-4-

benzofuryl), 7.91 (d, J_6,NH= 2.7 Hz, 1 H, H-6), 8.46 (s, 1 H, H-2), 12.56

(bd, J_NH,6= 2.2 Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 54.02 (CH₃O), 101.17 (C-4a),

102.54 (CH-3-benzofuryl), 105.87 (C-5), 110.72 (CH-7-benzofuryl),

120.92 (CH-4-benzofuryl), 123.15 (CH-6, CH-6-benzofuryl), 124.02

(CH-5-benzofuryl), 129.61 (C-3a-benzofuryl), 151.44 (C-2-benzofu-

ryl), 151.72 (CH-2), 153.59 (C-7a), 153.76 (C-7a-benzofuryl), 162.75

(C-4).

MS (ESI): m/z (%) = 216.1 (100) [M + H].

=

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₀O₂N₃: 216.0767; found:

216.0768.

5-(Furan-3-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (32b)

Compound 32b was prepared from 25b (250 mg, 0.72 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (120 mg, 77%) as a white solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 4.08 (s, 3 H, CH₃O), 6.94 (dd, J_4,5

=

1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.65 (d, J_6,NH= 2.5 Hz, 1 H, H-6),

7.67 (t, J_5,2= J_5,4= 1.7 Hz, 1 H, H-5-furyl), 8.07 (dd, J_2,5= 1.6 Hz, J_2,4= 0.9

Hz, 1 H, H-2-furyl), 8.37 (s, 1 H, H-2), 12.16 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 54.09 (CH₃O), 102.24 (C-4a),

106.86 (C-5), 110.67 (CH-4-furyl), 119.32 (C-3-furyl), 121.98 (CH-6),

139.94 (CH-2-furyl), 143.68 (CH-5-furyl), 151.29 (CH-2), 153.41 (C-

7a), 163.05 (C-4).

MS (EI): m/z (%) = 265.1 (100) [M], 266.1 (10) [M + H].

HRMS (EI): m/z [M] calcd for C₁₅H₁₁N₃O₂: 265.0851; found: 265.0851.

MS (ESI): m/z (%) = 216.1 (100) [M + H].

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimi-

dine (32f)

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₀O₂N₃: 216.0767; found:

216.0768.

Compound 32f was prepared from 25f (500 mg, 1.12 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (347 mg, 98%) as a white solid; mp >250 °C (dec).

4-Methoxy-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (32c)

Compound 32c was prepared from 25c (180 mg, 0.50 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (78 mg, 68%) as a yellowish solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 3.92 (s, 3 H, CH₃O), 7.41 (btd, J_8,9

=

J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₀H₇O), 7.45 (t, J_2,1= J_2,3= 7.6 Hz, 1

H, H-2-C₁₀H₇O), 7.52 (ddd, J_7,6= 8.2 Hz, J_7,8= 7.2 Hz, J_7,9= 1.4 Hz, 1 H,

H-7-C₁₀H₇O), 7.71 (dt, J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₀H₇O),

S

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Synthesis

7.80 (dd, J_3,2= 7.6 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₀H₇O), 7.87 (d, J_6,NH= 2.5

Hz, 1 H, H-6), 8.06 (dd, J_1,2= 7.7 Hz, J_1,3= 1.3 Hz, 1 H, H-1-C₁₀H₇O), 8.18

(ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-C₁₀H₇O), 8.46 (s, 1

H, H-2), 12.47 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 11.95 (CH₃S), 106.15 (C-5),

113.17 (CH-4-furyl), 113.72 (C-4a), 118.24 (C-3-furyl), 124.32 (CH-6),

140.62 (CH-2-furyl), 143.05 (CH-5-furyl), 149.49 (C-7a), 150.50 (CH-

2), 160.62 (C-4).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.65 (CH₃O), 103.05 (C-4a),

109.24 (C-5), 111.94 (CH-6-C₁₀H₇O), 119.27 (CH-1-C₁₀H₇O), 119.38

(C-4-C₁₀H₇O), 121.39 (CH-9-C₁₀H₇O), 123.18 (CH-2-C₁₀H₇O), 123.30

(CH-8-C₁₀H₇O), 123.79 (C-9b-C₁₀H₇O), 124.05 (C-9a-C₁₀H₇O), 124.58

(CH-6), 127.72 (CH-7-C₁₀H₇O), 128.94 (CH-3-C₁₀H₇O), 151.03 (CH-2),

153.15 (C-7a), 153.37 (C-4a-C₁₀H₇O), 155.64 (C-5a-C₁₀H₇O), 162.93

(C-4).

MS (ESI): m/z (%) = 232.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₀ON₃S: 232.0539; found:

232.0538.

4-(Methylsulfanyl)-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (33c)

Compound 33c was prepared from 26c (300 mg, 0.80 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (163 mg, 83%) as a white solid; mp 234–235 °C.

MS (EI): m/z (%) = 315.1 (100) [M], 316.1 (10) [M + H].

HRMS (EI): m/z [M] calcd for C₁₉H₁₃N₃O₂: 315.1008; found: 315.1008.

¹H NMR (401 MHz, DMSO-d₆): δ = 2.55 (s, 3 H, CH₃S), 7.14 (dd, J_4,5

5.2 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.20 (dd, J_3,4= 3.5 Hz, J_3,5= 1.2

Hz, 1 H, H-3-thienyl), 7.55 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thie-

nyl), 7.58 (s, 1 H, H-6), 8.62 (s, 1 H, H-2), 12.42 (bs, 1 H, NH).

¹³C NMR (101 MHz, DMSO-d₆): δ = 12.21 (CH₃S), 108.38 (C-5), 114.01

(C-4a), 125.86 (CH-6), 126.30 (CH-5-thienyl), 127.78 (CH-3-thienyl),

128.66 (CH-4-thienyl), 135.06 (C-2-thienyl), 149.55 (C-7a), 150.97

(CH-2), 161.15 (C-4).

=

4-Methoxy-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (32g)

Compound 32g was prepared from 25g (300 mg, 0.85 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (140 mg, 74%) as a white solid; mp 197–198 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 4.01 (s, 3 H, CH₃O), 7.26 (m, 1 H, H-

p-Ph), 7.39 (m, 2 H, H-m-Ph), 7.58 (s, 1 H, H-6), 7.67 (m, 2 H, H-o-Ph),

8.41 (s, 1 H, H-2), 12.27 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.54 (CH₃O), 102.14 (C-4a),

115.91 (C-5), 122.54 (CH-6), 126.19 (CH-p-Ph), 128.26 (CH-m-Ph),

128.57 (CH-o-Ph), 134.54 (C-i-Ph), 150.71 (CH-2), 153.35 (C-7a),

162.76 (C-4).

MS (ESI): m/z (%) = 248.0 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₀N₃S₂: 248.0310; found:

248.0310.

MS (ESI): m/z (%) = 226.1 (100) [M + H].

4-(Methylsulfanyl)-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (33d)

HRMS (ESI): m/z [M + H] calcd for C₁₃H₁₂ON₃: 226.0974; found:

226.0974.

Compound 33d was prepared from 26d (300 mg, 0.80 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (192 mg, 98%) as a white solid; mp 222–223 °C.

5-(Furan-2-yl)-4-(methylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine

¹H NMR (500 MHz, DMSO-d₆): δ = 2.45 (s, 3 H, CH₃S), 7.29 (dd, J_4,5

=

(33a)

Compound 33a was prepared from 26a (250 mg, 0.69 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (157 mg, 71%) as a white solid; mp 221–222 °C.

4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.51 (d, J_6,NH= 2.4 Hz, 1 H, H-6),

7.53 (dd, J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.59 (dd, J_5,4= 4.9

Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl), 8.60 (s, 1 H, H-2), 12.29 (bs, 1 H,

NH).

¹H NMR (401 MHz, DMSO-d₆): δ = 2.58 (s, 3 H, CH₃S), 6.58 (dd, J_4,3

=

3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 6.67 (dd, J_3,4= 3.3 Hz, J_3,5= 0.8 Hz,

1 H, H-3-furyl), 7.69 (S, 1 H, H-6), 7.74 (dd, J_5,4= 1.9 Hz, J_5,3= 0.8 Hz, 1

H, H-5-furyl), 8.62 (s, 1 H, H-2), 12.47 (bs, 1 H, NH).

¹³C NMR (101 MHz, DMSO-d₆): δ = 12.38 (CH₃S), 106.16 (C-5), 108.77

(CH-3-furyl), 111.82 (CH-4-furyl), 113.16 (C-4a), 125.35 (CH-6),

142.73 (CH-5-furyl), 147.82 (C-2-furyl), 149.71 (C-7a), 151.06 (CH-2),

161.25 (C-4).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 12.01 (CH₃S), 110.88 (C-5),

113.61 (C-4a), 123.48 (CH-2-thienyl), 124.37 (CH-6), 125.44 (CH-5-

thienyl), 130.19 (CH-4-thienyl), 134.27 (C-3-thienyl), 149.29 (C-7a),

150.45 (CH-2), 160.65 (C-4).

MS (EI): m/z (%) = 247.0 (100) [M], 248.0 (10) [M + H].

HRMS (EI): m/z [M] calcd for C₁₁H₉N₃S₂: 247.0238; found: 247.0236.

MS (ESI): m/z (%) = 232.1 (100) [M + H].

5-(Benzofuran-2-yl)-4-(methylsulfanyl)-7H-pyrrolo[2,3-d]pyrimi-

dine (33e)

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₀ON₃S: 232.05391; found:

232.05392.

Compound 33e was prepared from 26e (300 mg, 0.73 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (170 mg, 83%) as a white solid; mp 230–231 °C.

5-(Furan-3-yl)-4-(methylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine

¹H NMR (500 MHz, DMSO-d₆): δ = 2.60 (s, 3 H, CH₃O), 7.18 (d, J_3,7= 1.0

Hz, 1 H, H-3-benzofuryl), 7.26 (td, J_5,6= J_5,4= 7.4 Hz, J_5,7= 1.2 Hz, 1 H,

H-5-benzofuryl), 7.30 (bddd, J_6,7= 8.1 Hz, J_6,5= 7.2 Hz, J_6,4= 1.5 Hz, 1 H,

H-6-benzofuryl), 7.59 (bdq, J_7,6= 8.1 Hz, J_7,5= J_7,4= J_7,3= 1.0 Hz, 1 H, H-

7-benzofuryl), 7.67 (ddd, J_4,5= 7.5 Hz, J_4,6= 1.5 Hz, J_4,7= 0.7 Hz, 1 H, H-

4-benzofuryl), 7.95 (d, J_6,NH= 2.4 Hz, 1 H, H-6), 8.67 (s, 1 H, H-2), 12.68

(bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 12.31 (CH₃S), 104.42 (CH-3-ben-

zofuryl), 105.35 (C-5), 111.07 (CH-7-benzofuryl), 112.82 (C-4a),

120.97 (CH-4-benzofuryl), 123.15 (CH-5-benzofuryl), 124.16 (CH-6-

(33b)

Compound 33b was prepared from 26b (250 mg, 0.69 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (130 mg, 79%) as a white solid; mp 192–193 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.57 (s, 3 H, CH₃S), 6.73 (dd, J_4,5

1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.49 (d, J_6,NH= 2.5 Hz, 1 H, H-6),

7.74 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 7.84 (dd, J_2,5= 1.7 Hz, J_2,4= 0.9

Hz, 1 H, H-2-furyl), 8.59 (s, 1 H, H-2), 12.27 (bs, 1 H, NH).

=

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N. Sabat et al.

Special Topic

Synthesis

benzofuryl), 126.55 (CH-6), 129.10 (C-3a-benzofuryl), 149.82 (C-7a),

150.51 (C-2-benzofuryl), 151.05 (CH-2), 154.21 (C-7a-benzofuryl),

161.20 (C-4).

MS (CI): m/z (%) = 199.1 (25) [M], 200.1 (100) [M + H].

HRMS (CI): m/z [M + H] calcd for C₁₁H₁₀ON₃: 200.0824; found:

200.0816.

MS (EI): m/z (%) = 282.1 (100) [M + H].

5-(Furan-3-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine (34b)

HRMS (EI): m/z [M + H] calcd for C₁₅H₁₂ON₃S: 282.0695; found:

282.0696.

Compound 34b was prepared from 27b (143 mg, 0.43 mmol) by GPD′.

Reaction time: 48 h. Column chromatography (silica gel, 0–1%

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

ucts (49 mg, 57%) as a white crystalline solid; mp 229–230 °C.

5-(Dibenzo[b,d]furan-4-yl)-4-(methylsulfanyl)-7H-pyrrolo[2,3-d]-

pyrimidine (33f)

Compound 33f was prepared from 26f (500 mg, 1.08 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (330 mg, 93%) as a white solid; mp 280–281 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.60 (s, 3 H, CH₃-4), 6.76 (dd, J_4,5

=

1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.51 (s, 1 H, H-6), 7.77 (dd, J_5,4= J_5,2

= 1.7 Hz, 1 H, H-5-furyl), 7.84 (dd, J_2,5= 1.6 Hz, J_2,4= 0.9 Hz, 1 H, H-2-

furyl), 8.61 (s, 1 H, H-2), 12.17 (bs, 1 H, NH).

¹H NMR (500 MHz, DMSO-d₆): δ = 2.39 (s, 3 H, CH₃S), 7.41 (btd, J_8,9

=

J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₀H₇O), 7.46 (t, J_2,1= J_2,3= 7.5 Hz, 1

H, H-2-C₁₀H₇O), 7.49 (ddd, J_7,6= 8.3 Hz, J_7,8= 7.2 Hz, J_7,9= 1.4 Hz, 1 H,

H-7-C₁₀H₇O), 7.53 (dd, J_3,2= 7.4 Hz, J_3,1= 1.4 Hz, 1 H, H-3-C₁₀H₇O), 7.63

(bdt, J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.8 Hz, 1 H, H-6-C₁₀H₇O), 7.68 (d, J_6,NH= 2.5

Hz, 1 H, H-6), 8.15 (dd, J_1,2= 7.7 Hz, J_1,3= 1.4 Hz, 1 H, H-1-C₁₀H₇O), 8.18

(ddd, J_9,8= 7.7 Hz, J_9,7= 1.5 Hz, J_9,6= 0.8 Hz, 1 H, H-9-C₁₀H₇O), 8.64 (s, 1

H, H-2), 12.46 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 11.86 (CH₃S), 109.58 (C-5),

112.10 (CH-6-C₁₀H₇O), 114.86 (C-4a), 119.24 (C-4-C₁₀H₇O), 120.61

(CH-1-C₁₀H₇O), 121.55 (CH-9-C₁₀H₇O), 123.11 (CH-2-C₁₀H₇O), 123.42

(CH-8-C₁₀H₇O), 123.76 (C-9b-C₁₀H₇O), 124.16 (C-9a-C₁₀H₇O), 125.31

(CH-6), 127.88 (CH-7-C₁₀H₇O), 130.19 (CH-3-C₁₀H₇O), 149.41 (C-7a),

150.81 (CH-2), 154.54 (C-4a-C₁₀H₇O), 155.75 (C-5a-C₁₀H₇O), 161.21

(C-4).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 22.93 (CH₃-4), 106.35 (C-5),

113.05 (CH-4-furyl), 115.35 (C-4a), 118.99 (C-3-furyl), 124.73 (CH-6),

140.42 (CH-2-furyl), 143.46 (CH-5-furyl), 151.01 (CH-2), 151.43 (C-

7a), 158.91 (C-4).

MS (CI): m/z (%) = 199.1 (24) [M], 200.1 (100) [M + H].

HRMS (CI): m/z [M + H] calcd for C₁₁H₁₀ON₃: 200.0824; found:

200.0818.

4-Methyl-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (34c)

Compound 34c was prepared from 27c (136 mg, 0.39 mmol) by GPD′.

Reaction time: 96 h. Column chromatography (silica gel, 0–1%

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

uct (60 mg, 71%) as a white crystalline solid; mp 210–212 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.53 (s, 3 H, CH₃-4), 7.15 (dd, J_4,5

=

MS (EI): m/z (%) = 331.1 (100) [M], 332.1 (10) [M + H].

5.2 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.19 (dd, J_3,4= 3.5 Hz, J_3,5= 1.2

Hz, 1 H, H-3-thienyl), 7.56 (dd, J_5,4= 5.2 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thie-

nyl), 7.26 (s, 1 H, H-6), 8.64 (s, 1 H, H-2), 12.35 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 22.81 (CH₃-4), 108.23 (C-5),

115.38 (C-4a), 125.94 (CH-5-thienyl), 126.15 (CH-6), 127.75 (CH-4-

thienyl), 127.93 (CH-3-thienyl), 135.76 (C-2-thienyl), 151.23 (C-7a),

151.26 (CH-2), 158.87 (C-4).

HRMS (EI): m/z [M] calcd for C₁₉H₁₃N₃OS: 331.0779; found: 331.0778.

4-(Methylsulfanyl)-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (33g)

Compound 33g was prepared from 26g (256 mg, 0.70 mmol) by GPC.

Flash column chromatography (0–25% EtOAc/hexanes) gave the prod-

uct (140 mg, 82%) as a white solid; mp 237–239 °C.

¹H NMR (400 MHz, DMSO-d₆): δ = 2.53 (s, 3 H, CH₃S), 7.36 (m, 1 H, H-

p-Ph), 7.43 (m, 2 H, H-m-Ph), 7.50 (m, 3 H, H-6 and H-o-Ph), 8.62 (s, 1

H, H-2), 12.34 (bs, 1 H, NH).

¹³C NMR (101 MHz, DMSO-d₆): δ = 12.31 (CH₃S), 113.76 (C-4a),

116.59 (C-5), 124.53 (CH-6), 127.30 (CH-p-Ph), 128.29 (CH-m-Ph),

130.47 (CH-o-Ph), 134.60 (C-i-Ph), 149.71 (CH-2), 150.69 (C-7a),

160.91 (C-4).

MS (CI): m/z (%) = 215.1 (22) [M], 216.1 (100) [M + H].

HRMS (CI): m/z [M + H] calcd for C₁₁H₁₀N₃S: 216.0595; found:

216.0586.

4-Methyl-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (34d)

Compound 34d was prepared from 27d (202 mg, 0.59 mmol) by GPD′.

Reaction time:

7 d. Column chromatography (silica gel, 0–1%

MS (ESI): m/z (%) = 242.1 (100) [M + H].

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

uct (55 mg, 44%) as a white crystalline solid; mp 254–255 °C.

HRMS (ESI): m/z [M + H] calcd for C₁₃H₁₂N₃S: 242.0746; found:

242.0746.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.52 (s, 3 H, CH₃-4), 7.30 (dd, J_4,5

4.9 Hz, J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.54 (s, 1 H, H-6), 7.54 (dd, J_2,5

3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 7.63 (dd, J_5,4= 4.9 Hz, J_5,2= 3.0

=

5-(Furan-2-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine (34a)

Compound 34a was prepared from 27a (119 mg, 0.36 mmol) by GPD′′.

Reaction time: 48 h. Column chromatography (silica gel, 0–1.5%

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

uct (61 mg, 85%) as a white crystalline solid; mp 206–208 °C.

Hz, 1 H, H-5-thienyl), 8.62 (s, 1 H, H-2), 12.19 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 23.01 (CH₃-4), 111.07 (C-5),

115.29 (C-4a), 123.19 (CH-2-thienyl), 124.80 (CH-6), 125.99 (CH-5-

thienyl), 130.08 (CH-4-thienyl), 135.13 (C-3-thienyl), 150.98 (CH-2),

151.23 (C-7a), 158.92 (C-4).

¹H NMR (500 MHz, DMSO-d₆): δ = 2.64 (s, 3 H, CH₃-4), 6.59 (dd, J_4,3

=

3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 6.61 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz,

1 H, H-3-furyl), 7.75 (s, 1 H, H-6), 7.76 (dd, J_5,4= 1.8 Hz, J_5,3= 0.9 Hz, 1

H, H-5-furyl), 8.64 (s, 1 H, H-2), 12.38 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 23.14 (CH₃-4), 106.00 (C-5),

107.83 (CH-3-furyl), 111.66 (CH-4-furyl), 114.51 (C-4a), 125.75 (CH-

6), 142.52 (CH-5-furyl), 148.52 (C-2-furyl), 151.33 (CH-2), 151.39 (C-

7a), 159.08 (C-4).

MS (CI): m/z (%) = 215.1 (24) [M], 216.1 (100) [M + H].

HRMS (CI): m/z [M + H] calcd for C₁₁H₁₀N₃S: 216.0595; found:

216.0594.

U

N. Sabat et al.

Special Topic

Synthesis

5-(Benzofuran-2-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine (34e)

MS (CI): m/z (%) = 209.1 (77) [M], 210.1 (100) [M + H].

Compound 34e was prepared from 27e (164 mg, 0.43 mmol) by GPD′.

Reaction time: 72 h. Purification by reverse-phase HPFC (C-18, 0–

100% MeOH/H₂O) then recrystallization (H₂O/MeOH 2:1) gave the

product (86 mg, 59%) as a white crystalline solid; mp 257–258 °C.

HRMS (CI): m/z [M + H] calcd for C₁₃H₁₂N₃: 210.1031; found:

210.1034.

5-(Furan-2-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine

(35a)

¹H NMR (500 MHz, DMSO-d₆): δ = 2.77 (s, 3 H, CH₃-4), 7.10 (d, J_3,7

=

1.0 Hz, 1 H, H-3-benzofuryl), 7.26 (td, J_5,6= J_5,4= 7.3 Hz, J_5,7= 1.3 Hz, 1

H, H-5-benzofuryl), 7.30 (bddd, J_6,7= 8.0 Hz, J_6,5= 7.3 Hz, J_6,4= 1.5 Hz, 1

H, H-6-benzofuryl), 7.61 (bdq, J_7,6= 8.0 Hz, J_7,5= J_7,4= J_7,3= 0.8 Hz, 1 H,

H-7-benzofuryl), 7.65 (ddd, J_4,5= 7.3 Hz, J_4,6= 1.6 Hz, J_4,7= 0.8 Hz, 1 H,

H-4-benzofuryl), 8.01 (s, 1 H, H-6), 8.69 (s, 1 H, H-2), 12.59 (vbs, 1 H,

NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 23.67 (CH₃-4), 103.66 (CH-3-

benzofuryl), 105.48 (C-5), 111.06 (CH-7-benzofuryl), 114.39 (C-4a),

120.88 (CH-4-benzofuryl), 123.25 (CH-5-benzofuryl), 124.07 (CH-6-

benzofuryl), 127.31 (CH-6), 129.10 (C-3a-benzofuryl), 151.33 (C-2-

benzofuryl), 151.55 (CH-2), 151.72 (C-7a), 154.28 (C-7a-benzofuryl),

159.29 (C-4).

Compound 35a was prepared from 28a (270 mg, 0.75 mmol) by GPD.

Flash column chromatography (70–80% EtOAc/hexanes) then recrys-

tallization (MeOH, gave the product (120 mg, 69%) as a yellowish sol-

id; mp 208–209 °C.

IR (KBr): 3342, 3138, 1617, 1576, 1392, 1093, 968, 794, 700, 551 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 3.97 (s, 3 H, CH₃O-4), 6.15 (bs, 2 H,

NH₂), 6.48 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1 H, H-4-furyl), 6.77 (dd, J_3,4

.

=

3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.12 (d, J_6,NH= 2.4 Hz, 1 H, H-6),

7.54 (dd, J_5,4= 1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 11.30 (bd, J_NH,6= 2.3

Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.07 (CH₃O-4), 93.51 (C-4a),

105.64 (CH-3-furyl), 106.72 (C-5), 111.60 (CH-4-furyl), 116.47 (CH-

6), 140.69 (CH-5-furyl), 149.85 (C-2-furyl), 155.79 (C-7a), 159.88 (C-

2), 163.26 (C-4).

MS (CI): m/z (%) = 249.1 (98) [M], 250.1 (100) [M + H].

HRMS (CI): m/z [M + H] calcd for C₁₅H₁₂N₃O: 250.0980; found:

250.0981.

MS (ESI): m/z (%) = 231.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄O₂: 231.0876; found:

231.0876.

5-(Dibenzo[b,d]furan-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimi-

dine (34f)

Compound 34f was prepared from 27f (174 mg, 0.41 mmol) by GPD′′.

Reaction time: 7 d. Column chromatography (silica gel, 0–1.5%

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

uct (102 mg, 84%) as a white crystalline solid; mp 304–306 °C.

5-(Furan-3-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine

(35b)

Compound 35b was prepared from 28b (340 mg, 0.94 mmol) by GPD.

Flash column chromatography (70–80% EtOAc/hexanes) then recrys-

tallization (MeOH) gave the product (169 mg, 78%) as an orange solid;

mp 223–224 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.24 (s, 3 H, CH₃-4), 7.42 (btd, J_8,9

=

J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₀H₇O), 7.49 (t, J_2,1= J_2,3= 7.6 Hz, 1

H, H-2-C₁₀H₇O), 7.51 (ddd, J_7,6= 8.3 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H,

H-7-C₁₀H₇O), 7.57 (dd, J_3,2= 7.4 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₀H₇O), 7.66

(dt, J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₀H₇O), 7.75 (s, 1 H, H-6),

IR (KBr): 3316, 3102, 1629, 1575, 1391, 1316, 1098, 1013, 776, 595

cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 3.96 (s, 3 H, CH₃O), 6.08 (bs, 2 H,

NH₂), 6.84 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.14 (d, J_6,NH

8.19 (dd, J_1,2= 7.7 Hz, J_1,3= 1.3 Hz, 1 H, H-1-C₁₀H₇O), 8.20 (ddd, J_9,8

7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-C₁₀H₇O), 8.69 (s, 1 H, H-2),

=

12.43 (bs, 1 H, NH).

2.3 Hz, 1 H, H-6), 7.61 (t, J_5,2= J_5,4= 1.7 Hz, 1 H, H-5-furyl), 7.98 (dd, J_2,5

= 1.6 Hz, J_2,4= 0.9 Hz, 1 H, H-2-furyl), 11.14 (d, J_NH,6= 2.3 Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 52.99 (CH₃O-4), 94.72 (C-4a),

106.53 (C-5), 110.11 (CH-4-furyl), 117.25 (CH-6), 119.74 (C-3-furyl),

139.03 (CH-2-furyl), 142.99 (CH-5-furyl), 155.89 (C-7a), 159.64 (C-2),

163.26 (C-4).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 21.99 (CH₃-4), 110.00 (C-5),

112.22 (CH-6-C₁₀H₇O), 116.29 (C-4a), 120.14 (C-4-C₁₀H₇O), 120.65

(CH-1-C₁₀H₇O), 121.79 (CH-9-C₁₀H₇O), 123.69 (CH-2,8-C₁₀H₇O),

124.08 (C-9a-C₁₀H₇O), 124.24 (C-9b-C₁₀H₇O), 126.19 (CH-6), 128.15

(CH-7-C₁₀H₇O), 129.88 (CH-3-C₁₀H₇O), 151.42 (CH-2), 151.69 (C-7a),

154.26 (C-4a-C₁₀H₇O), 155.82 (C-5a-C₁₀H₇O), 159.28 (C-4).

MS (ESI): m/z (%) = 231.1 (100) [M + H].

MS (ESI): m/z (%) = 300.2 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄O₂: 231.0876; found:

HRMS (ESI): m/z [M + H] calcd for C₁₉H₁₄N₃O: 300.11314; found:

231.0876.

300.11318.

4-Methoxy-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-

amine (35c)

4-Methyl-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (34g)

Compound 34g was prepared from 27g (350 mg, 0.90 mmol) by

GPD′′. Reaction time: 5 d. Column chromatography (silica gel, 0–1.5%

MeOH/CHCl₃) then recrystallization (H₂O/MeOH 2:1) gave the prod-

uct (171 mg, 90%) as a white crystalline solid; mp 240–242 °C.

Compound 35c was prepared from 28c (508 mg, 1.35 mmol) by GPD.

Flash column chromatography (70–80% EtOAc/hexanes) then recrys-

tallization (MeOH, gave the product (239 mg, 72%) as a white solid;

mp 266–267 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.45 (s, 3 H, CH₃-4), 7.35 (m, 1 H, H-

p-Ph), 7.43 (m, 2 H, H-m-Ph), 7.49 (m, 2 H, H-o-Ph), 7.53 (s, 1 H, H-6),

8.63 (s, 1 H, H-2), 12.24 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 23.20 (CH₃-4), 115.12 (C-4a),

116.47 (C-5), 124.69 (CH-6), 126.95 (CH-p-Ph), 128.36 (CH-m-Ph),

130.07 (CH-o-Ph), 135.13 (C-i-Ph), 150.96 (CH-2), 151.41 (C-7a),

158.81 (C-4).

IR (KBr): 3337, 3103, 1624, 1575, 1393, 1316, 1093, 826, 697, 568 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 3.94 (s, 3 H, CH₃O-4), 6.14 (bs, 2 H,

NH₂), 7.02 (dd, J_4,5= 5.2 Hz, J_4,3= 3.6 Hz, 1 H, H-4-thienyl), 7.09 (s, 1 H,

H-6), 7.30 (dd, J_5,4= 5.2 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.36 (dd, J_3,4

3.5 Hz, J_5,3= 1.2 Hz, 1 H, H-3-thienyl), 11.30 (bs, 1 H, NH).

.

=

V

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 52.93 (CH₃O-4), 94.64 (C-4a),

109.47 (C-5), 117.69 (CH-6), 123.04 (CH-5-thienyl), 124.41 (CH-3-

thienyl), 127.63 (CH-4-thienyl), 137.63 (C-2-thienyl), 155.83 (C-7a),

159.72 (C-2), 163.31 (C-4).

IR (KBr): 3362, 3122, 1634, 1576, 1450, 1302, 1197, 1096, 734, 631

cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 3.84 (s, 3 H, CH₃O), 6.15 (bs, 2 H,

NH₂), 7.40 (btd, J_8,9= J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₂H₇O), 7.41

(t, J_2,1= J_2,3= 7.7 Hz, 1 H, H-2-C₁₂H₇O), 7.43 (d, J_6,NH= 2.4 Hz, 1 H, H-6),

7.51 (ddd, J_7,6= 8.2 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₂H₇O), 7.72

(dt, J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₂H₇O), 7.81 (dd, J_3,2= 7.6

Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₂H₇O), 7.99 (dd, J_1,2= 7.7 Hz, J_1,3= 1.3 Hz, 1

H, H-1-C₁₂H₇O), 8.15 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H,

H-9-C₁₂H₇O), 11.47 (d, J_NH,6= 2.4 Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 52.96 (CH₃O-4), 95.64 (C-4a),

109.42 (C-5), 111.86 (CH-6-C₁₂H₇O), 118.43 (CH-1-C₁₂H₇O), 120.23

(C-4-C₁₂H₇O), 120.35 (CH-6), 121.24 (CH-9-C₁₂H₇O), 123.02 and

123.14 (CH-2,8-C₁₂H₇O), 123.61 (C-9b-C₁₂H₇O), 124.08 (C-9a-C₁₂H₇O),

127.51 (CH-7-C₁₂H₇O), 128.41 (CH-3-C₁₂H₇O), 153.12 (C-4a-C₁₂H₇O),

155.52 (C-5a-C₁₂H₇O), 155.88 (C-7a), 159.70 (C-2), 163.46 (C-4)..

MS (ESI): m/z (%) = 247.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄OS: 247.0648; found:

247.0647.

4-Methoxy-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-

amine (35d)

Compound 35d was prepared from 28d (480 mg, 1.27 mmol) by GPD.

Flash column chromatography (70–80% EtOAc/hexanes) then recrys-

tallization (MeOH) gave the product (190 mg, 61%) as a brownish sol-

id; mp 260–261 °C.

IR (KBr): 3336, 3099, 1624, 1570, 1389, 1307, 1095, 854, 772, 571 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 3.96 (s, 3 H, CH₃O), 6.10 (bs, 2 H,

NH₂), 7.20 (d, J_6,NH= 2.3 Hz, 1 H, H-6), 7.46 (dd, J_4,5= 5.0 Hz, J_4,2= 1.6

Hz, 1 H, H-4-thienyl), 7.47 (dd, J_5,4= 5.0 Hz, J_5,2= 2.7 Hz, 1 H, H-5-thie-

MS (ESI): m/z (%) = 331.1 (100) [M + H], 353.1 (10) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₉H₁₅N₄O₂: 331.1189; found:

331.1191.

nyl), 7.72 (dd, J_2,5= 2.7 Hz, J_2,4= 1.6 Hz, 1 H, H-2-thienyl), 11.21 (d, J_NH,6

=

2.2 Hz, 1 H, NH).

4-Methoxy-5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine (35g)

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.07 (CH₃O-4), 94.85 (C-4a),

111.32 (C-5), 118.01 (CH-6), 1119.57 (CH-2-thienyl), 125.35 and

127.90 (CH-4,5-thienyl), 135.68 (C-3-thienyl), 155.75 (C-7a), 159.49

(C-2), 163.40 (C-4).

Compound 35g was prepared from 28g (185 mg, 0.50 mmol) by GPD.

Flash column chromatography (70–80% EtOAc/hexanes) then recrys-

tallization (MeOH) gave the product (65 mg, 54%) as a white solid; mp

226–227 °C.

MS (ESI): m/z (%) = 247.1 (100) [M + H].

IR (KBr): 3312, 3118, 1630, 1574, 1379, 1314, 1091, 971, 785, 608 cm^–1

.

HRMS (ESI): m/z [M + H] calcd for C₁₁H₁₁N₄OS: 247.0648; found:

247.0648.

¹H NMR (500 MHz, DMSO-d₆): δ = 3.89 (s, 3 H, CH₃O-4), 6.08 (bs, 2 H,

NH₂), 7.05 (d, J_6,NH= 2.4 Hz, 1 H, H-6), 7.19 (m, 1 H, H-p-Ph), 7.33 (m, 2

H, H-m-Ph), 7.61 (m, 2 H, H-o-Ph), 11.26 (bd, J_NH,6= 2.3 Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 52.92 (CH₃O-4), 94.99 (C-4a),

116.16 (C-5), 118.01 (CH-6), 125.66 (CH-p-Ph), 128.04 and 128.14

(CH-o,m-Ph), 135.40 (C-i-Ph), 156.12 (C-7a), 159.51 (C-2), 163.41 (C-

4).

5-(Benzofuran-2-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-

amine (35e)

Compound 35e was prepared from 28e (400 mg, 0.97 mmol) by GPD.

Flash column chromatography (80–90% EtOAc/hexanes) then recrys-

tallization (MeOH) gave the product (145 mg, 56%) as a yellowish sol-

id; mp 238–239 °C.

MS (ESI): m/z (%) = 241.1 (100) [M + H].

IR (KBr): 3344, 3117, 1612, 1579, 1452, 1321, 1092, 791, 739, 557 cm^–1

.

HRMS (ESI): m/z [M + H] calcd for C₁₃H₁₃N₄O: 241.1083; found:

241.1084.

¹H NMR (500 MHz, DMSO-d₆): δ = 4.06 (s, 3 H, CH₃O-4), 6.25 (bs, 2 H,

NH₂), 7.19 (btd, J_5,6= J_5,4= 7.3 Hz, J_5,7= 1.4 Hz, 1 H, H-5-benzofuryl),

7.22 (btd, J_6,7= J_6,5= 7.2 Hz, J_6,4= 1.7 Hz, 1 H, H-6-benzofuryl), 7.26 (d,

J_3,7= 1.1 Hz, 1 H, H-3-benzofuryl), 7.42 (d, J_6,NH= 2.5 Hz, 1 H, H-6),

7.49 (m, 1 H, H-7-benzofuryl), 7.59 (m, 1 H, H-4-benzofuryl), 11.55

(d, J_NH,6= 2.5 Hz, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 53.29 (CH₃O-4), 93.71 (C-4a),

101.52 (CH-3-benzofuryl), 106.01 (C-5), 110.51 (CH-7-benzofuryl),

118.97 (CH-6), 120.60 (CH-4-benzofuryl), 122.96 (CH-5-benzofuryl),

123.60 (CH-6-benzofuryl), 129.77 (C-3a-benzofuryl), 152.35 (C-2-

benzofuryl), 153.59 (C-7a-benzofuryl), 156.31 (C-7a), 160.15 (C-2),

163.30 (C-4).

5-(Furan-2-yl)-4-methoxy-2-methyl-7H-pyrrolo[2,3-d]pyrimidine

(36a)

Compound 36a was prepared from 29a (240 mg, 0.67 mmol) by GPC.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (140 mg, 91%) as a white solid; mp

246–247 °C.

IR (KBr): 3115, 2949, 1569, 1347, 1288, 1207, 1102, 820, 772, 604 cm^–1

.

¹H NMR (600 MHz, DMSO-d₆): δ = 2.53 (s, 3 H, CH₃-2), 4.06 (s, 3 H,

CH₃O-4), 6.52 (dd, J_4,3= 3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 6.85 (dd,

J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.52 (d, J_6,NH= 2.5 Hz, 1 H, H-

6), 7.60 (dd, J_5,4= 1.8 Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 12.06 (bs, 1 H,

NH).

MS (ESI): m/z (%) = 281.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₅H₁₃N₄O₂: 281.1033; found:

281.1033.

¹³C NMR (150.9 MHz, DMSO-d₆): δ = 25.58 (CH₃-2), 53.41 (CH₃O-4),

98.41 (C-4a), 106.34 (CH-3-furyl), 106.41 (C-5), 111.75 (CH-4-furyl),

119.99 (CH-6), 141.19 (CH-5-furyl), 149.19 (C-2-furyl), 153.93 (C-7a),

160.22 (C-2), 162.43 (C-4).

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-7H-pyrrolo[2,3-d]pyrimi-

din-2-amine (35f)

MS (ESI): m/z (%) = 230.1 (100) [M + H].

Compound 35f was prepared from 28f (540 mg, 1.17 mmol) by GPD.

Flash column chromatography (80–90% EtOAc/hexanes) then recrys-

tallization (MeOH) gave the product (190 mg, 51%) as a brownish sol-

id; mp 257–258 °C.

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₂N₃O₂: 230.0924; found:

230.0924.

W

N. Sabat et al.

Special Topic

Synthesis

5-(Furan-3-yl)-4-methoxy-2-methyl-7H-pyrrolo[2,3-d]pyrimidine

5-(Benzofuran-2-yl)-4-methoxy-2-methyl-7H-pyrrolo[2,3-d]py-

(36b)

rimidine (36e)

Compound 36b was prepared from 29b (310 mg, 0.86 mmol) by GPD.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (125 mg, 61%) as a yellowish solid;

mp 242–243 °C.

Compound 36e was prepared from 29e (300 mg, 0.81 mmol) by GPC.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (174 mg, 77%) as a yellowish solid;

mp 111–112 °C.

IR (KBr): 3101, 2947, 1570, 1348, 1296, 1105, 1035, 817, 777, 592 cm^–1

.

IR (KBr): 3099, 2940, 1571, 1344, 1272, 1099, 1017, 798, 707, 614 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.53 (s, 3 H, CH₃-2), 4.05 (s, 3 H,

CH₃O-4), 6.92 (dd, J_4,5= 1.8 Hz, J_4,2= 0.9 Hz, 1 H, H-4-furyl), 7.55 (d,

J_6,NH= 2.4 Hz, 1 H, H-6), 7.66 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 8.06

(dd, J_2,5= 1.6 Hz, J_2,4= 0.9 Hz, 1 H, H-2-furyl), 11.90 (bs, 1 H, NH).

¹H NMR (500 MHz, DMSO-d₆): δ = 2.56 (s, 3 H, CH₃-2), 4.14 (s, 3 H,

CH₃O-4), 7.21 (btd, J_5,6= J_5,4= 7.2 Hz, J_5,7= 1.3 Hz, 1 H, H-5-benzofu-

ryl), 7.25 (btd, J_6,7= J_6,5= 7.6 Hz, J_6,4= 1.5 Hz, 1 H, H-6-benzofuryl),

7.35 (d, J_3,7= 1.1 Hz, 1 H, H-3-benzofuryl), 7.53 (bdq, J_7,6= 7.6 Hz, J_7,5

=

J_7,4= J_7,3= 1.1 Hz, 1 H, H-7-benzofuryl), 7.62 (bd, J_4,5= 7.4 Hz, 1 H, H-4-

benzofuryl), 7.81 (s, 1 H, H-6), 12.31 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.58 (CH₃-2), 53.36 (CH₃O-4),

99.49 (C-4a), 106.28 (C-5), 110.23 (CH-4-furyl), 119.25 (C-3-furyl),

120.76 (CH-6), 139.43 (CH-2-furyl), 143.22 (CH-5-furyl), 154.08 (C-

7a), 159.76 (C-2), 162.38 (C-4).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.60 (CH₃-2), 53.70 (CH₃O-4),

98.76 (C-4a), 102.24 (CH-3-benzofuryl), 105.67 (C-5), 110.63 (CH-7-

benzofuryl), 120.80 (CH-4-benzofuryl), 122.30 (CH-6), 123.07 (CH-5-

benzofuryl), 123.88 (CH-6-benzofuryl), 129.61 (C-3a-benzofuryl),

151.66 (C-2-benzofuryl), 153.69 (C-7a-benzofuryl), 154.41 (C-7a),

160.66 (C-2), 162.44 (C-4).

MS (ESI): m/z (%) = 230.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₂N₃O₂: 230.0924; found:

230.0924.

MS (ESI): m/z (%) = 280.1 (100) [M + H].

4-Methoxy-2-methyl-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimi-

dine (36c)

HRMS (ESI): m/z [M + H] calcd for C₁₆H₁₄N₃O₂: 280.1081; found:

280.1082.

Compound 36c was prepared from 29c (350 mg, 0.93 mmol) by GPC.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (208 mg, 87%) as a white solid; mp

219–220 °C.

5-(Dibenzo[b,d]furan-4-yl)-4-methoxy-2-methyl-7H-pyrrolo[2,3-

d]pyrimidine (36f)

Compound 36f was prepared from 29f (496 mg, 1.08 mmol) by GPC.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (295 mg, 83%) as a white solid; mp

290–291 °C.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.58 (s, 3 H, CH₃-2), 3.90 (s, 3 H,

CH₃O-4), 7.41 (td, J_8,9= J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H, H-8-C₁₂H₇O), 7.44

(t, J_2,1= J_2,3= 7.6 Hz, 1 H, H-2-C₁₂H₇O), 7.52 (ddd, J_7,6= 8.2 Hz, J_7,8= 7.3

Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₂H₇O), 7.72 (dt, J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.9

Hz, 1 H, H-6-C₁₂H₇O), 7.79 (s, 1 H, H-6), 7.81 (dd, J_3,2= 7.6 Hz, J_3,1= 1.3

Hz, 1 H, H-3-C₁₂H₇O), 8.04 (dd, J_1,2= 7.7 Hz, J_1,3= 1.3 Hz, 1 H, H-1-

IR (KBr): 3101, 2945, 1568, 1351, 1289, 1100, 1021, 792, 710, 615 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.54 (s, 3 H, CH₃-2), 4.03 (s, 3 H,

CH₃O-4), 7.06 (dd, J_4,5= 5.1 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.37 (dd,

J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.42 (dd, J_3,4= 3.5 Hz, J_3,5

1.2 Hz, 1 H, H-3-thienyl), 7.51 (s, 1 H, H-6), 12.06 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.56 (CH₃-2), 53.30 (CH₃O-4),

99.40 (C-4a), 109.07 (C-5), 121.31 (CH-6), 123.84 (CH-5-thienyl),

125.09 (CH-3-thienyl), 127.72 (CH-4-thienyl), 136.76 (C-2-thienyl),

153.93 (C-7a), 159.96 (C-2), 162.43 (C-4).

.

=

MS (ESI): m/z (%) = 246.1 (100) [M + H].

C

₁₂H₇O), 8.17 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-

₁₂H₇O), 12.21 (bs, 1 H, NH).

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₂N₃OS: 246.0696; found:

246.0696.

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.63 (CH₃-2), 53.35 (CH₃O-4),

100.59 (C-4a), 109.09 (C-5), 111.91 (CH-6-C₁₂H₇O), 119.03 (C-4-

C

₁₂H₇O), 121.33 (CH-9-C₁₂H₇O), 123.12 and 123.23 (CH-2,8-C₁₂H₇O),

4-Methoxy-2-methyl-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimi-

123.72 (CH-6), 123.73 (C-9b-C₁₂H₇O), 124.03 (C-9a-C₁₂H₇O), 127.64

(C-7-C₁₂H₇O), 128.75 (CH-3-C₁₂H₇O), 153.25 (C-4a-C₁₂H₇O), 154.00

(C-7a), 155.59 (C-5a-C₁₂H₇O), 159.85 (C-2), 162.63 (C-4).

dine (36d)

Compound 36d was prepared from 29d (450 mg, 1.20 mmol) by GPD.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (171 mg, 58%) as a white solid; mp

312–313 °C.

MS (ESI): m/z (%) = 330.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₂₀H₁₆N₃O₂: 330.1237; found:

IR (KBr): 3099, 2950, 2828, 1570, 1347, 1288, 1102, 1006, 777, 605

330.1238.

cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.54 (s, 3 H, CH₃-2), 4.04 (s, 3 H,

CH₃O-4), 7.52 (dd, J_5,4= 5.0 Hz, J_5,2= 2.7 Hz, 1 H, H-5-thienyl), 7.54 (dd,

J_4,5= 5.0 Hz, J_4,2= 1.6 Hz, 1 H, H-4-thienyl), 7.61 (s, 1 H, H-6), 7.81 (dd,

J_2,5= 2.7 Hz, J_2,4= 1.6 Hz, 1 H, H-2-thienyl), 11.96 (bs, 1 H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.35 (CH₃-2), 53.35 (CH₃O-4),

99.53 (C-4a), 110.86 (C-5), 120.34 (CH-2-thienyl), 121.44 (CH-6),

125.58 (CH-4-thienyl), 128.00 (CH-5-thienyl), 135.03 (C-3-thienyl),

154.04 (C-7a), 159.59 (C-2), 162.41 (C-4).

4-Methoxy-2-methyl-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine (36g)

Compound 36g was prepared from 29g (368 mg, 0.90 mmol) by GPD.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) then recrystalli-

zation (MeOH) gave the product (134 mg, 62%) as a white solid; mp

227–228 °C.

IR (KBr): 3111, 2948, 2840, 1560, 1335, 1188, 1007, 835, 728, 616 cm^–

1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.55 (s, 3 H, CH₃-2), 3.98 (s, 3 H,

CH₃O-4), 7.24 (m, 1 H, H-p-Ph), 7.37 (m, 2 H, H-m-Ph), 7.47 (s, 1 H, H-

6), 7.66 (m, 2 H, H-o-Ph), 12.02 (bs, 1 H, NH).

MS (ESI): m/z (%) = 246.1 (100) [M + H].

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₂N₃OS: 246.0696; found:

246.0696.

X

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 25.23 (CH₃-2), 53.27 (CH₃O-4),

99.75 (C-4a), 115.75 (C-5), 121.62 (CH-6), 126.04 (CH-p-Ph), 128.24

(CH-m-Ph), 128.40 (CH-o-Ph), 134.75 (C-i-Ph), 154.24 (C-7a), 159.51

(C-2), 162.49 (C-4).

5-(Thiophen-3-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

(37d)

Compound 37d was prepared from 32d (80 mg, 0.35 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(55 mg, 73%) as a white solid; mp >300 °C (dec).

MS (ESI): m/z (%) = 240.1 (100) [M + H].

¹H NMR (500 MHz, DMSO-d₆): δ = 7.47 (dd, J_5,4= 5.0 Hz, J_5,2= 3.0 Hz, 1

H, H-5-thienyl), 7.50 (d, J_6,NH= 2.6 Hz, 1 H, H-6), 7.66 (dd, J_4,5= 5.0 Hz,

J_4,2= 1.3 Hz, 1 H, H-4-thienyl), 7.85 (d, J_2,NH= 3.4 Hz, 1 H, H-2), 8.43

(dd, J_2,5= 3.0 Hz, J_2,4= 1.3 Hz, 1 H, H-2-thienyl), 11.86 (bs, 1 H, NH-1),

12.01 (bs, 1 H, NH-7).

HRMS (ESI): m/z [M + H] calcd for C₁₄H₁₄N₃O: 240.1131; found:

240.1132.

5-(Furan-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

(37a)

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 104.61 (C-4a), 115.59 (C-5),

118.39 (CH-6), 121.17 (CH-2-thienyl), 125.41 (CH-5-thienyl), 127.48

(CH-4-thienyl), 135.05 (C-3-thienyl), 143.36 (CH-2), 149.29 (C-7a),

159.14 (C-4).

Compound 37a was prepared from 32a (40 mg, 0.18 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(30 mg, 82%) as a white solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 6.48 (dd, J_4,3= 3.3 Hz, J_4,5= 1.9 Hz, 1

H, H-4-furyl), 7.31 (d, J_6,NH= 2.6 Hz, 1 H, H-6), 7.33 (dd, J_3,4= 3.3 Hz, J_3,5

= 1.0 Hz, 1 H, H-3-furyl), 7.56 (dd, J_5,4= 1.9 Hz, J_5,3= 0.9 Hz, 1 H, H-5-

furyl), 7.86 (d, J_2,NH= 3.8 Hz, 1 H, H-2), 11.88 (bs, 1 H, NH-1), 12.10 (bs,

1 H, NH-7).

MS (ESI): m/z (%) = 218.2 (11) [M + H], 240.2 (89) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₀H₈ON₃S: 218.0382; found:

218.0382.

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 103.50 (C-4a), 107.62 (CH-3-fu-

ryl), 110.89 (C-5), 111.64 (CH-4-furyl), 116.49 (CH-6), 141.00 (CH-5-

furyl), 144.46 (CH-2), 149.16 (C-7a), 149.30 (C-2-furyl), 158.66 (C-4).

5-(Benzofuran-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-

one (37e)

Compound 37e was prepared from 32e (80 mg, 0.30 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(67 mg, 89%) as a white solid; mp >250 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 7.20 (td, J_5,6= J_5,4= 7.3 Hz, J_5,7= 1.2

Hz, 1 H, H-5-benzofuryl), 7.23 (bddd, J_6,7= 8.0 Hz, J_6,5= 7.2 Hz, J_6,4= 1.5

Hz, 1 H, H-6-benzofuryl), 7.51 (bdq, J_7,6= 8.0 Hz, J_7,5= J_7,4= J_7,3= 1.0 Hz,

MS (ESI): m/z (%) = 224.04 (100) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₀H₇O₂N₃Na: 224.0430; found:

224.0430.

5-(Furan-3-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

(37b)

1 H, H-7-benzofuryl), 7.60 (d, J_6,NH= 2.7 Hz, 1 H, H-6), 7.62 (dm, J_4,5

=

7.5 Hz, 1 H, H-4-benzofuryl), 7.38 (d, J_3,7= 1.1 Hz, 1 H, H-3-benzofu-

ryl), 7.92 (d, J_2,NH= 3.7 Hz, 1 H, H-2), 12.06 (bd, J_NH,2= 3.3 Hz, 1 H, NH-

1), 13.34 (bs, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 103.54 (CH-3-benzofuryl),

104.12 (C-4a), 110.10 (C-5), 110.61 (CH-7-benzofuryl), 118.84 (CH-6),

120.86 (CH-4-benzofuryl), 123.02 (CH-5-benzofuryl), 123.83 (CH-6-

benzofuryl), 129.60 (C-3a-benzofuryl), 144.92 (CH-2), 149.80 (C-7a),

151.76 (C-2-benzofuryl), 153.74 (C-7a-benzofuryl), 158.73 (C-4).

Compound 37b was prepared from 32b (92 mg, 0.43 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(32 mg, 37%) as a white solid; mp >250 °C (dec).

¹H NMR (401 MHz, DMSO-d₆): δ = 6.97 (dd, J_4,5= 1.9 Hz, J_4,2= 0.8 Hz, 1

H, H-4-furyl), 7.40 (s, 1 H, H-6), 7.62 (t, J_5,2= J_5,4= 1.7 Hz, 1 H, H-5-

furyl), 7.84 (s, 1 H, H-2), 8.50 (bd, J_2,5= 1.7 Hz, 1 H, H-2-furyl), 11.82

and 11.95 (2 bs, 2 × 1 H, NH).

¹³C NMR (101 MHz, DMSO-d₆): δ = 104.91 (C-4a), 109.94 (CH-4-fu-

ryl), 111.19 (C-5), 117.89 (CH-6), 119.44 (C-3-furyl), 140.95 (CH-2-fu-

ryl), 143.29 (CH-5-furyl), 144.27 (CH-2), 149.42 (C-7a), 159.28 (C-4).

MS (ESI): m/z (%) = 252.2 (50.8) [M + H], 274.2 (49.2) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₄H₁₀O₂N₃: 252.0767; found:

252.0768.

MS (ESI): m/z (%) = 224.04 (100) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₀H₇O₂N₃Na: 224.0430; found:

224.0430.

5-(Dibenzo[b,d]furan-4-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimi-

din-4-one (37f)

Compound 37f was prepared from 32f (290 mg, 0.92 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(175 mg, 63%) as a white solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 7.41 (t, J_2,1= J_2,3= 7.7 Hz, 1 H, H-2-

5-(Thiophen-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one

(37c)

Compound 37c was prepared from 32c (70 mg, 0.33 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(50 mg, 76%) as a white solid; mp >200 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 7.02 (dd, J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1

H, H-4-thienyl), 7.31 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl),

7.34 (s, 1 H, H-6), 7.85 (s, 1 H, H-2), 7.90 (dd, J_3,4= 3.6 Hz, J_3,5= 1.2 Hz,

1 H, H-3-thienyl), 11.66–12.36 (m, 2 H, NH-1,7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 104.32 (C-4a), 113.95 (C-5),

117.94 (CH-6), 123.41 (CH-5-thienyl), 126.13 (CH-3-thienyl), 127.71

(CH-4-thienyl), 136.73 (C-2-thienyl), 144.27 (CH-2), 149.26 (C-7a),

158.76 (C-4).

C

₁₀H₇O), 7.41 (td, J_8,9= J_8,7= 7.5 Hz, J_8,6= 0.9 Hz, 1 H, H-8-C₁₀H₇O), 7.52

(ddd, J_7,6= 8.3 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-C₁₀H₇O), 7.76 (dt,

J_6,7= 8.2 Hz, J_6,8= J_6,9= 0.9 Hz, 1 H, H-6-C₁₀H₇O), 7.85 (s, 1 H, H-6), 7.93

(s, 1 H, H-2), 7.99 (dd, J_1,2= 7.6 Hz, J_1,3= 1.3 Hz, 1 H, H-1-C₁₀H₇O), 8.16

(ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-C₁₀H₇O), 8.50 (dd,

J_3,2= 7.7 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₀H₇O), 11.94 and 12.32 (2 bs, 2 × 1

H, NH).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 105.25 (C-4a), 112.03 (CH-6-

C

₁₀H₇O), 114.02 (C-5), 118.75 (CH-1-C₁₀H₇O), 119.28 (C-4-C₁₀H₇O),

121.26 (CH-9-C₁₀H₇O), 121.51 (CH-6), 123.11 and 123.31 (CH-2,8-

C

₁₀H₇O), 123.63 (C-9b-C₁₀H₇O), 124.08 (C-9a-C₁₀H₇O), 127.55 (CH-7-

₁₀H₇O), 129.37 (CH-3-C₁₀H₇O), 144.29 (CH-2), 149.43 (C-7a), 152.82

MS (ESI): m/z (%) = 240.0 (100) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₀H₇ON₃NaS: 240.0202; found:

240.0202.

(C-4a-C₁₀H₇O), 155.47 (C-5a-C₁₀H₇O), 158.87 (C-4).

Y

N. Sabat et al.

Special Topic

Synthesis

MS (ESI): m/z (%) = 302.3 (61) [M + H], 324.3 (39) [M + Na].

IR (KBr): 3187, 3021, 2869, 1690, 1573, 1400, 1137, 770, 686, 506 cm^–

.

¹H NMR (500 MHz, DMSO-d₆): δ = 6.17 (bs, 2 H, NH₂), 6.93 (s, 1 H, H-

1

HRMS (ESI): m/z [M + H] calcd for C₁₈H₁₂O₂N₃: 302.0924; found:

302.0925.

6), 6.97 (dd, J_4,5= 5.1 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.22 (dd, J_5,4

=

5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.88 (dd, J_3,4= 3.5 Hz, J_3,5= 1.2

Hz, 1 H, H-3-thienyl), 10.38 (bs, 1 H, NH-3), 11.19 (bs, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 97.02 (C-4a), 113.63 (C-5),

114.43 (CH-6), 122.40 (CH-5-thienyl), 125.50 (CH-3-thienyl), 127.56

(CH-4-thienyl), 137.63 (C-2-thienyl), 152.53 (C-7a), 152.81 (C-2),

159.19 (C-4).

5-Phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (37g)

Compound 37g was prepared from 32g (75 mg, 0.33 mmol) by GPE.

Flash column chromatography (0–5% MeOH/CH₂Cl₂) gave the product

(63 mg, 90%) as a white solid; mp >250 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 7.19 (m, 1 H, H-p-Ph), 7.32 (m, 2 H,

H-m-Ph), 7.39 (d, J_6,NH= 2.6 Hz, 1 H, H-6), 7.86 (d, J_2,NH= 3.4 Hz, 1 H, H-

2), 7.94 (m, 2 H, H-o-Ph), 11.84 (bs, 1 H, NH-1), 12.08 (bs, 1 H, NH-7).

MS (ESI): m/z (%) = 233.0 (40) [M + H], 255.0 (100) [M + Na].

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 104.66 (C-4a), 118.74 (CH-6),

120.24 (C-5), 125.92 (CH-p-Ph), 128.10 and 128.11 (CH-m,o-Ph),

134.44 (C-i-Ph), 143.85 (CH-2), 149.54 (C-7a), 158.86 (C-4).

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄OS: 233.0491; found:

233.0491.

2-Amino-5-(thiophen-3-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimi-

din-4-one (38d)

MS (ESI): m/z (%) = 212.1 (49) [M + H], 234.1 (51) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₂H₉ON₃Na: calcd 234.0637;

found: 234.0637.

Compound 38d (63 mg, 68%) was obtained as a white solid from 35d

(98 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3181, 3020, 2858, 1691, 1574, 1402, 1130, 777, 684, 507 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 6.12 (bs, 2 H, NH₂), 7.08 (d, J_6,NH

.

2-Amino-5-(furan-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-

4-one (38a)

=

2.4 Hz, 1 H, H-6), 7.41 (dd, J_4,5= 5.0 Hz, J_4,2= 1.2 Hz, 1 H, H-4-thienyl),

7.55 (dd, J_5,4= 5.0 Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl), 8.37 (dd, J_2,5= 3.0

Hz, J_2,4= 1.2 Hz, 1 H, H-2-thienyl), 10.33 (bs, 1 H, NH-3), 11.10 (bd,

J_NH,6= 2.3 Hz, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 97.36 (C-4a), 115.22 (CH-6),

115.35 (C-5), 120.46 (CH-2-thienyl), 125.30 (CH-5-thienyl), 127.30

(CH-4-thienyl), 135.81 (C-3-thienyl), 152.68 and 152.74 (C-7a, 2),

159.73 (C-4).

Compound 38a (56 mg, 64%) was obtained as a brownish solid from

35a (86 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3198, 3006, 2887, 1686, 1570, 1405, 1139, 774, 516 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 6.19 (bs, 2 H, NH₂), 6.44 (dd, J_4,3

3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 6.91 (bs, 1 H, H-6), 7.25 (dd, J_3,4

=

3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.49 (dd, J_5,4= 1.8 Hz, J_5,3= 0.9 Hz,

1 H, H-5-furyl), 10.39 (bs, 1 H, NH-3), 11.20 (bs, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 96.08 (C-4a), 106.87 (CH-3-fu-

ryl), 110.52 (C-5), 111.51 (CH-4-furyl), 113.17 (CH-6), 140.46 (CH-5-

furyl), 150.04 (C-2-furyl), 152.40 (C-7a), 152.98 (C-2), 159.12 (C-4).

MS (ESI): m/z (%) = 233.1 (30) [M + H], 255.1 (100) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄OS: 233.0491; found:

233.0491.

MS (ESI): m/z (%) = 217.0 (70) [M + H], 239.0 (100) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄O₂: 217.0720; found:

217.0719.

2-Amino-5-(benzofuran-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]py-

rimidin-4-one (38e)

Compound 38e (82 mg, 77%) was obtained as a greenish solid from

35e (101 mg, 0.36 mmol) by GPE; mp >300 °C (dec).

2-Amino-5-(furan-3-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-

4-one (38b)

IR (KBr): 3349, 3123, 1624, 1577, 1345, 1257, 1175, 783, 684, 547 cm^–1

.

Compound 38b (50 mg, 58%) was obtained as a brownish solid from

35b (93 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

¹H NMR (500 MHz, DMSO-d₆): δ = 6.25 (bs, 2 H, NH₂), 7.17 (m, 1 H, H-

5-benzofuryl), 7.17–7.22 (m, 2 H, H-6-benzofuryl, H-6), 7.47 (dm, J_7,6

= 7.4 Hz, 1 H, H-7-benzofuryl), 7.56 (dm, J_4,5= 7.0 Hz, 1 H, H-4-benzo-

furyl), 7.78 (d, J_3,7= 1.1 Hz, 1 H, H-3-benzofuryl), 10.52 (bs, 1 H, NH-

3), 11.45 (d, J_NH,6= 2.0 Hz, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 96.55 (C-4a), 102.86 (CH-3-ben-

zofuryl), 109.79 (C-5), 110.57 (CH-7-benzofuryl), 115.86 (CH-6),

120.69 (CH-4-benzofuryl), 123.00 (CH-5-benzofuryl), 123.62 (CH-6-

benzofuryl), 129.85 (C-3a-benzofuryl), 152.55 (C-2-benzofuryl),

153.12 and 153.32 (C-7a, 2), 153.73 (C-7a-benzofuryl), 159.26 (C-4).

IR (KBr): 3202, 2879, 2758, 1667, 1570, 1388, 1152, 1020, 777, 486

cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 6.11 (bs, 2 H, NH₂), 6.86 (dd, J_4,5

=

1.9 Hz, J_4,2= 0.8 Hz, 1 H, H-4-furyl), 6.97 (d, J_6,NH= 2.4 Hz, 1 H, H-6),

7.56 (t, J_5,4= J_5,2= 1.7 Hz, 1 H, H-5-furyl), 8.44 (bd, J_2,5= 1.6 Hz, 1 H, H-

2-furyl), 10.23 (bs, 1 H, NH-3), 11.05 (bd, J_NH,6= 1.8 Hz, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 97.29 (C-4a), 109.50 (CH-4-fu-

ryl), 110.44 (C-5), 114.26 (CH-6), 119.73 (C-3-furyl), 140.36 (CH-2-fu-

ryl), 142.83 (CH-5-furyl), 152.44 (C-7a), 152.71 (C-2), 159.45 (C-4).

MS (ESI): m/z (%) = 267.2 (40) [M + H], 289.2 (100) [M + Na].

MS (ESI): m/z (%) = 217.1 (30) [M + H], 239.1 (100) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₄H₁₁N₄O₂: 267.0876; found:

267.0877.

HRMS (ESI): m/z [M + H] calcd for C₁₀H₉N₄O₂: 217.0720; found:

217.0720.

2-Amino-5-(dibenzo[b,d]furan-4-yl)-3,7-dihydro-4H-pyrrolo[2,3-

d]pyrimidin-4-one (38f)

2-Amino-5-(thiophen-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimi-

din-4-one (38c)

Compound 38f (62 mg, 73%) was obtained as a brownish solid from

35f (90 mg, 0.27 mmol) by GPE; mp >300 °C (dec).

Compound 38c (54 mg, 65%) was obtained as a yellowish solid from

35c (90 mg, 0.36 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3324, 3257, 1643, 1451, 1195, 842, 783, 750, 631 cm^–1

.

Z

N. Sabat et al.

Special Topic

Synthesis

¹H NMR (500 MHz, DMSO-d₆): δ = 6.21 (bs, 2 H, NH₂), 7.37 (t, J_2,1= J_2,3

7.6 Hz, 1 H, H-2-C₁₂H₇O), 7.40 (btd, J_8,9= J_8,7= 7.5 Hz, J_8,6= 1.0 Hz, 1 H,

H-8-C₁₂H₇O), 7.51 (ddd, J_7,6= 8.2 Hz, J_7,8= 7.3 Hz, J_7,9= 1.4 Hz, 1 H, H-7-

=

¹H NMR (500 MHz, DMSO-d₆): δ = 2.30 (s, 3 H, CH₃-2), 6.94 (dd, J_4,5

1.8 Hz, J_4,2= 0.8 Hz, 1 H, H-4-furyl), 7.29 (s, 1 H, H-6), 7.60 (t, J_5,4= J_5,2

1.7 Hz, 1 H, H-5-furyl), 8.49 (bd, J_2,5= 1.7 Hz, 1 H, H-2-furyl), 11.27–

=

C₁₂H₇O), 7.58 (d, J_6,NH= 2.2 Hz, 1 H, H-6), 7.76 (dt, J_6,7= 8.2 Hz, J_6,8= J_6,9

=

12.11 (m, 2 H, NH-1,7).

0.8 Hz, 1 H, H-6-C₁₂H₇O), 7.92 (dd, J_1,2= 7.6 Hz, J_1,3= 1.3 Hz, 1 H, H-1-

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.92 (CH₃-2), 102.29 (C-4a),

109.60 (CH-4-furyl), 110.60 (C-5), 116.92 (CH-6), 119.31 (C-3-furyl),

140.59 (CH-2-furyl), 142.98 (CH-5-furyl), 149.87 (C-7a), 153.13 (C-2),

159.73 (C-4).

C

₁₂H₇O), 8.13 (ddd, J_9,8= 7.7 Hz, J_9,7= 1.4 Hz, J_9,6= 0.7 Hz, 1 H, H-9-

₁₂H₇O), 8.67 (dd, J_3,2= 7.7 Hz, J_3,1= 1.3 Hz, 1 H, H-3-C₁₂H₇O), 10.45

(bs, 1 H, NH-3), 11.45 (bd, J_NH,6= 2.1 Hz, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 97.86 (C-4a), 112.20 (CH-6-

MS (ESI): m/z (%) = 214.1 (100) [M – H].

C

₁₂H₇O), 113.95 (C-5), 118.24 (CH-1-C₁₂H₇O), 118.90 (CH-6), 120.18

HRMS (ESI): m/z [M – H] for C₁₁H₈N₃O₂: 214.0622; found: 214.0619.

(C-4-C₁₂H₇O), 121.39 (CH-9-C₁₂H₇O), 123.30 and 123.48 (CH-2,8-

C

₁₂H₇O), 123.70 (C-9b-C₁₂H₇O), 124.35 (C-9a-C₁₂H₇O), 127.65 (CH-7-

₁₂H₇O), 129.19 (CH-3-C₁₂H₇O), 152.79 (C-4a-C₁₂H₇O), 153.03 and

2-Methyl-5-(thiophen-2-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimi-

din-4-one (39c)

153.07 (C-2,7a), 155.60 (C-5a-C₁₂H₇O), 159.63 (C-4).

Compound 39c (56 mg, 87%) was obtained as a yellowish solid from

36c (69 mg, 0.30 mmol) by GPE; mp 409–410 °C.

MS (ESI): m/z (%) = 317.1 (95) [M + H], 339.1 (100) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₈H₁₃N₄O₂: 317.1033; found:

317.1034.

IR (KBr): 3093, 2923, 1651, 1600, 1551, 1297, 1099, 808, 787, 681 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.30 (s, 3 H, CH₃-2), 7.01 (dd, J_4,5

.

=

5.1 Hz, J_4,3= 3.5 Hz, 1 H, H-4-thienyl), 7.25 (d, J_6,NH= 2.5 Hz, 1 H, H-6),

7.29 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1 H, H-5-thienyl), 7.91 (dd, J_3,4= 3.5

Hz, J_3,5= 1.2 Hz, 1 H, H-3-thienyl), 11.78 (bs, 1 H, NH-1), 11.86 (bs, 1 H,

NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.89 (CH₃-2), 101.98 (C-4a),

113.68 (C-5), 117.15 (CH-6), 123.09 (CH-5-thienyl), 125.97 (CH-3-

thienyl), 127.64 (CH-4-thienyl), 136.92 (C-2-thienyl), 149.93 (C-7a),

153.40 (C-2), 159.41 (C-4).

2-Amino-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-

one (38g)

Compound 38g (68 mg, 62%) was obtained as a white solid from 35g

(116 mg, 0.48 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3180, 3017, 2859, 1688, 1573, 1401, 1130, 779, 683, 506 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 6.13 (bs, 2 H, NH₂), 7.02 (m, 1 H, H-

p-Ph), 7.18 (m, 2 H, H-m-Ph), 7.29 (s, 1 H, H-6), 7.94 (m, 2 H, H-o-Ph),

10.36 (bs, 1 H, NH-3), 11.19 (bs, 1 H, NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 97.29 (C-4a), 115.33 (CH-6),

119.81 (C-5), 125.50 (CH-p-Ph), 127.60 (CH-o-Ph), 128.03 (CH-m-Ph),

135.12 (C-i-Ph), 151.66 (C-7a), 152.60 (C-2), 159.36 (C-4).

.

MS (ESI): m/z (%) = 232.1 (15) [M + H], 254.0 (100) [M + Na].

HRMS (ESI): m/z [M + Na] calcd for C₁₁H₉N₃ONaS: 254.0359; found:

254.0359.

MS (ESI): m/z (%) = 227.1 (50) [M + H], 249.0 (100) [M + Na].

2-Methyl-5-(thiophen-3-yl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimi-

din-4-one (39d)

HRMS (ESI): m/z [M + H] calcd for C₁₂H₁₁N₄O: 227.0927; found:

227.0927.

Compound 39d (54 mg, 58%) was obtained as a white solid from 36d

(100 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

5-(Furan-2-yl)-2-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-

4-one (39a)

IR (KBr): 3091, 2920, 1647, 1601, 1548, 1288, 1082, 809, 787, 672 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.31 (s, 3 H, CH₃-2), 7.41 (s, 1 H, H-

6), 7.47 (dd, J_5,4= 5.0 Hz, J_5,2= 3.0 Hz, 1 H, H-5-thienyl), 7.64 (dd, J_4,5

5.0 Hz, J_4,2= 1.2 Hz, 1 H, H-4-thienyl), 8.43 (dd, J_2,5= 3.0 Hz, J_2,4= 1.2

Hz, 1 H, H-2-thienyl), 11.43–12.00 (m, 2 H, NH-1,7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.86 (CH₃-2), 102.25 (C-4a),

115.30 (C-5), 117.66 (CH-6), 120.93 (CH-2-thienyl), 125.35 (CH-5-

thienyl), 127.36 (CH-4-thienyl), 135.22 (C-3-thienyl), 149.99 (C-7a),

153.08 (C-2), 159.82 (C-4).

.

Compound 39a (78 mg, 91%) was obtained as a yellowish solid from

36a (98 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

=

IR (KBr): 3099, 2912, 1664, 1600, 1452, 1301, 911, 816, 775, 673 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.30 (s, 3 H, CH₃-2), 6.47 (dd, J_4,3

.

=

3.3 Hz, J_4,5= 1.8 Hz, 1 H, H-4-furyl), 7.22 (d, J_6,NH= 2.6 Hz, 1 H, H-6),

7.32 (dd, J_3,4= 3.3 Hz, J_3,5= 0.9 Hz, 1 H, H-3-furyl), 7.54 (dd, J_5,4= 1.8

Hz, J_5,3= 0.9 Hz, 1 H, H-5-furyl), 11.78 (bs, 1 H, NH-3), 11.87 (bs, 1 H,

NH-7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.96 (CH₃-2), 101.19 (C-4a),

107.46 (CH-3-furyl), 110.64 (C-5), 111.60 (CH-4-furyl), 115.82 (CH-

6), 140.87 (CH-5-furyl), 149.48 (C-2-furyl), 149.83 (C-7a), 153.66 (C-

2), 159.37 (C-4).

MS (ESI): m/z (%) = 230.1 (100) [M – H].

HRMS (ESI): m/z [M – H] for C₁₁H₈N₃OS: 230.0394; found: 230.0390.

5-(Benzofuran-2-yl)-2-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]py-

rimidin-4-one (39e)

MS (ESI): m/z (%) = 214.1 (100) [M – H].

Compound 39e (70 mg, 77%) was obtained as a yellowish solid from

36e (96 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

HRMS (ESI): m/z [M – H] for C₁₁H₈N₃O₂: 214.0622; found: 214.0618.

IR (KBr): 3094, 2928, 1643, 1599, 1452, 1255, 1115, 818, 792, 742 cm^–1

¹H NMR (500 MHz, DMSO-d₆): δ = 2.33 (s, 3 H, CH₃-2), 7.19 (td, J_5,6

.

5-(Furan-3-yl)-2-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-

4-one (39b)

=

J_5,4= 7.3 Hz, J_5,7= 1.2 Hz, 1 H, H-5-benzofuryl), 7.23 (m, 1 H, H-6-ben-

zofuryl), 7.50 (m, 1 H, H-7-benzofuryl), 7.51 (d, J_6,NH= 2.5 Hz, 1 H, H-

6), 7.61 (m, 1 H, H-4-benzofuryl), 7.86 (d, J_3,7= 1.1 Hz, 1 H, H-3-ben-

zofuryl), 11.94 (bs, 1 H, NH-1), 12.11 (bs, 1 H, NH-7).

Compound 39b (53 mg, 61%) was obtained as a yellowish solid from

36b (100 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3100, 2922, 1662, 1604, 1448, 1307, 1035, 814, 787, 673 cm^–1

.

AA

N. Sabat et al.

Special Topic

Synthesis

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.97 (CH₃-2), 101.76 (C-4a),

103.34 (CH-3-benzofuryl), 109.82 (C-5), 110.56 (CH-7-benzofuryl),

118.18 (CH-6), 120.79 (CH-4-benzofuryl), 122.97 (CH-5-benzofuryl),

123.73 (CH-6-benzofuryl), 129.62 (C-3a-benzofuryl), 150.46 (C-7a),

151.93 (C-2-benzofuryl), 153.71 (C-7a-benzofuryl), 154.17 (C-2),

159.40 (C-4).

Acknowledgment

The authors thank Dr. Petr Džubák and Dr. Marián Hajdúch (Palacky

University Olomouc) for cytostatic activity testing.

Supporting Information

MS (ESI): m/z (%) = 264.1 (100) [M – H].

Supporting information for this article is available online at

HRMS (ESI): m/z [M – H] for C₁₅H₁₀N₃O₂: 264.0779; found: 264.0773.

https://doi.org/10.1055/s-0036-1588443.

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5-(Dibenzo[b,d]furan-4-yl)-2-methyl-3,7-dihydro-4H-pyrrolo[2,3-

d]pyrimidin-4-one (39f)

References

Compound 39f (79 mg, 83%) was obtained as a yellowish solid from

36f (99 mg, 0.30 mmol) by GPE; mp >300 °C (dec).

(1) Reviews: (a) De Coen, L. M.; Henbaert, T. S. A.; Garcia, D.;

Stevens, C. V. Chem. Rev. 2016, 116, 80. (b) Tumkevicius, S.;

Dodonova, J. Chem. Heterocycl. Compd. 2012, 48, 258.

IR (KBr): 3055, 2911, 2826, 1650, 1613, 1452, 1196, 933, 819, 743 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.63 (s, 3 H, CH₃-2), 7.38–7.44 (m, 2

H, H-2,8-C₁₂H₇O), 7.52 (bt, J_7,6= J_7,8= 7.8 Hz, 1 H, H-7-C₁₂H₇O), 7.77

(bd, J_6,7= 8.2 Hz, 1 H, H-6-C₁₂H₇O), 7.81 (s, 1 H, H-6), 7.98 (bd, J_1,2= 7.5

Hz, 1 H, H-1-C₁₂H₇O), 8.16 (bd, J_9,8= 7.7 Hz, 1 H, H-9-C₁₂H₇O), 8.58

(bd, J_3,2= 7.6 Hz, 1 H, H-3-C₁₂H₇O), 11.10–12.68 (m, 2 H, NH-1,7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.91 (CH₃-2), 102.83 (C-4a),

111.98 (CH-6-C₁₂H₇O), 113.76 (C-5), 118.51 (CH-1-C₁₂H₇O), 119.44

(C-4-C₁₂H₇O), 120.93 (CH-6), 121.19 (CH-9-C₁₂H₇O), 123.08 and

123.24 (CH-2,8-C₁₂H₇O), 123.56 (C-9b-C₁₂H₇O), 124.05 (C-9a-C₁₂H₇O),

127.46 (C-7-C₁₂H₇O), 129.20 (CH-3-C₁₂H₇O), 150.16 (C-7a), 152.69 (C-

4a-C₁₂H₇O), 153.45 (C-2), 155.41 (C-5a-C₁₂H₇O), 159.58 (C-4).

(2) Examples: (a) Lawhorn, B. G.; Philp, J.; Zhao, Y.; Louer, C.;

Hammond, M.; Cheung, M.; Fries, H.; Graves, A. P.; Shewchuk,

L.; Wang, L.; Cottom, J. E.; Qi, H.; Zhao, H.; Totoritis, R.; Zhang,

G.; Schwartz, B.; Li, H.; Sweitzer, S.; Holt, D. A.; Gatto, G. J. Jr.;

Kallander, L. S. J. Med. Chem. 2015, 58, 7431. (b) Henderson, J. L.;

Kormos, B. L.; Hayward, M. M.; Coffman, K. J.; Jasti, J.;

Kurumbail, R. G.; Wager, T. T.; Verhoest, P. R.; Noell, G. S.; Chen,

Y.; Needle, E.; Berger, Z.; Steyn, S. J.; Houle, C.; Hirst, W. D.;

Galatsis, P. J. Med. Chem. 2015, 58, 419. (c) O’Brien, N. J.;

Brzozowski, M.; Buskes, M. J.; Deady, L. W.; Abbott, B. M. Bioorg.

Med. Chem. 2014, 22, 3879. (d) Smith, D. E.; Marquez, I.;

Lokensgard, M. E.; Rheingold, A. L.; Hecht, D. A.; Gustafson, J. L.

Angew. Chem. Int. Ed. 2015, 54, 11754. (e) Novotny, C. J.; Pollari,

S.; Park, J. H.; Lemmon, M. A.; Shen, W.; Shokat, K. M. Nat. Chem.

Biol. 2016, 12, 923. (f) Lee, J.-H.; Shin, S. C.; Seo, S. H.; Seo, Y. H.;

Jeong, N.; Kim, C.-W.; Kim, E. E.; Keum, G. Bioorg. Med. Chem.

Lett. 2017, 27, 237.

MS (ESI): m/z (%) = 316.1 (100) [M + H], 338.1 (100) [M + Na].

HRMS (ESI): m/z [M + H] calcd for C₁₉H₁₄N₃O₂: 316.1081; found:

316.1081.

2-Methyl-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-

one (39g)

(3) (a) Tumkevicius, S.; Dodonova, J.; Kazlauskas, K.; Masevisius, V.;

Skardziute, L.; Jursenas, S. Tetrahedron Lett. 2010, 51, 3902.

(b) Urbonas, R. V.; Poskus, V.; Bucevicius, J.; Dodonova, J.;

Tumkevicius, S. Synlett 2013, 24, 1383. (c) Dodonova, J.;

Tumkevicius, S. RSC Adv. 2014, 4, 35966. (d) Dodonova, J.;

Skardziute, L.; Kazlauskas, K.; Jursenas, S.; Tumkevicius, S. Tetra-

hedron 2012, 68, 329. (e) Bucevicius, J.; Tumkevicius, S. Synthesis

2015, 47, 2100. (f) Prieur, V.; Rubio-Martınez, J.; Font-Bardia,

M.; Guillaumet, G.; Pujol, M. D. Eur. J. Org. Chem. 2014, 1514.

(g) Prieur, V.; Heindler, N.; Rubio-Martinez, J.; Guillaumet, G.;

Pujol, M. D. Tetrahedron 2015, 71, 1207. (h) Krömer, M.; Klečka,

M.; Slavětínská, L.; Klepetářová, B.; Hocek, M. Eur. J. Org. Chem.

2014, 7203. (i) Klečka, M.; Poštová Slavětínská, L.; Hocek, M. Eur.

J. Org. Chem. 2015, 7943. (j) Sabat, N.; Slavětínská, L.;

Klepetářová, B.; Hocek, M. J. Org. Chem. 2016, 81, 9507.

Compound 39g (55 mg, 52%) was obtained as a white solid from 36g

(102 mg, 0.40 mmol) by GPE; mp >300 °C (dec).

IR (KBr): 3090, 2919, 1648, 1600, 1548, 1288, 1086, 802, 785, 677 cm^–1

.

¹H NMR (500 MHz, DMSO-d₆): δ = 2.32 (s, 3 H, CH₃-2), 7.17 (m, 1 H, H-

p-Ph), 7.32 (s, 1 H, H-6), 7.32 (m, 2 H, H-m-Ph), 7.96 (m, 2 H, H-o-Ph),

11.50–12.10 (m, 2 H, NH-1,7).

¹³C NMR (125.7 MHz, DMSO-d₆): δ = 20.84 (CH₃-2), 102.31 (C-4a),

118.03 (CH-6), 119.93 (C-5), 125.79 (CH-p-Ph), 127.92 (CH-o-Ph),

128.10 (CH-m-Ph), 134.60 (C-i-Ph), 150.29 (C-7a), 153.00 (C-2),

159.59 (C-4).

MS (ESI): m/z (%) = 224.1 (100) [M – H].

HRMS (ESI): m/z [M – H] calcd for C₁₃H₁₀N₃O: 224.0829; found:

224.0827.

(4) Sabat, N.; Nauš, P.; Matyašovský, J.; Dziuba, D.; Poštová

Slavětínská, L.; Hocek, M. Synthesis 2016, 48, 1029.

(5) Bourderioux, A.; Nauš, P.; Perlíková, P.; Pohl, R.; Pichová, I.;

Votruba, I.; Džubák, P.; Konečný, P.; Hajdúch, M.; Stray, K. M.;

Wang, T.; Ray, A. S.; Feng, J. Y.; Birkus, G.; Cihlar, T.; Hocek, M.

J. Med. Chem. 2011, 54, 5498.

(6) Snášel, J.; Nauš, P.; Dostál, J.; Hnízda, A.; Fanfrlík, J.; Brynda, J.;

Bourderioux, A.; Dušek, M.; Dvořáková, H.; Stolaříková, J.;

Zábranská, H.; Pohl, R.; Konečný, P.; Džubák, P.; Votruba, I.;

Hajdúch, M.; Řezáčová, P.; Veverka, V.; Hocek, M.; Pichová, I.

J. Med. Chem. 2014, 57, 8268.

Funding Information

This work was supported by the Academy of Sciences of the Czech Re-

public (RVO 61388963 and the Praemium Academiae award to M. Ho-

cek), by the Czech Science Foundation (16-0011785 to N. S. and M.

H.), by the Czech Health Research Council (15-31984A to S. S.), and by

Gilead Sciences, Inc.Ac

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N. Sabat et al.

Special Topic

Synthesis

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Znojek, P.; Nová, A.; Harvanová, M.; Džubák, P.; Šiller, M.;

Hlaváč, J.; Hajdúch, M.; Hocek, M. Mol. Cancer Ther. 2016, 15,

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Article Doi

Synthesis of 2,6-Substituted 7-(Het)aryl-7-deazapurine Nucleobases (2,4-Disubstituted 5-(Het)aryl-pyrrolo[2,3- d ]pyrimidines)

DOI: 10.1055/s-0036-1588443

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Article abstract of DOI:10.1055/s-0036-1588443

Full text of DOI:10.1055/s-0036-1588443

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