Synthesis of 4-aryl-, 2,4-diaryl- and 2,4,7-triarylpyrrolo[2,3-d] pyrimidines by a combination of the Suzuki cross-coupling and N-arylation reactions

Article abstract of DOI:10.1016/j.tet.2011.10.040

A simple and facile synthesis of novel 4-aryl-2-chloro-, 2,4-diaryl- and 2,4,7-triarylpyrrolo[2,3-d]pyrimidines with various aryl and heteroaryl assemblies in the heterocyclic framework by a combination of Suzuki cross-coupling and N-arylation reactions of 2,4-dichloropyrrolo[2,3-d]pyrimidine with arylboronic acids and haloarenes are described. A majority of the synthesized compounds were found to emit in a near UV-blue spectral range with fluorescence quantum yields up to 67%. The impact of aryl groups attached to the pyrrole ring of pyrrolopyrimidine derivatives on optical properties is discussed.

Full text of DOI:10.1016/j.tet.2011.10.040

Tetrahedron 68 (2012) 329e339
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Tetrahedron
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Synthesis of 4-aryl-, 2,4-diaryl- and 2,4,7-triarylpyrrolo[2,3-d]pyrimidines by
a combination of the Suzuki cross-coupling and N-arylation reactions
,
Jelena Dodonova a, Lina Skardziute b, Karolis Kazlauskas b, Saulius Jursenas b, Sigitas Tumkevicius a
*
a Department of Organic Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania
b Institute of Applied Research, Vilnius University, Sauletekio 9-III, LT-10222 Vilnius, Lithuania
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2011
Received in revised form 14 September 2011
Accepted 10 October 2011
Available online 19 October 2011
A simple and facile synthesis of novel 4-aryl-2-chloro-, 2,4-diaryl- and 2,4,7-triarylpyrrolo[2,3-d]py-
rimidines with various aryl and heteroaryl assemblies in the heterocyclic framework by a combination of
Suzuki cross-coupling and N-arylation reactions of 2,4-dichloropyrrolo[2,3-d]pyrimidine with arylbor-
onic acids and haloarenes are described. A majority of the synthesized compounds were found to emit in
a near UV-blue spectral range with fluorescence quantum yields up to 67%. The impact of aryl groups
attached to the pyrrole ring of pyrrolopyrimidine derivatives on optical properties is discussed.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Pyrrolo[2,3-d]pyrimidines
Suzuki reaction
N-Arylation
Oligoarylenes
Fluorescence
1. Introduction
heterocycle. Our synthetic strategy towards the target compounds
was based on a combination of the palladium-catalyzed Suzuki
The introduction of a heteroaryl moiety into extended
p
-sys-
cross-coupling reaction of 2,4-dichloropyrolo[2,3-d]pyrimidine (1)
with arylboronic acids and copper-catalyzed N-arylations of pyr-
rolo[2,3-d]pyrimidines with aryl halides. The Suzuki cross-coupling
reaction has received much attention in the past years due to its
versatility in the CeC bond formation and construction of biaryl
skeleton.13 However, a literature survey on the arylpyrrolo[2,3-d]
pyrimidines revealed that the Suzuki reaction in a pyrrolo[2,3-d]
pyrimidine series is explored insufficiently. To the best of our
knowledge, only few examples were reported on the application of
the palladium-catalyzed cross-coupling reactions for the arylation
of a pyrrole6b,14 and pyrimidine rings9a,12,15 of pyrrolo[2,3-d]py-
rimidine and there were no data on a site-selectivity of the Suzuki
coupling of 2,4-dichloropyrrolo[2,3-d]pyrimidine.
tems often brings about a number of interesting properties that are
useful in the development of advanced electronic and photonic
materials.1 Owing to the light-emitting,2 self-assembling3 and
complex forming4 properties with metal ions or organic molecules
such materials are of interest in biological, chemical and materials
science. Otherwise, arylpyrrolo[2,3-d]pyrimidines were found to
display a wide range of biological activities, such as antimicrobial,5
inhibition of protein kinases6 and dihydrofolate reductase,7 an-
tagonist effects to receptors,8 cytostatic and antiproliferative ef-
fects,9 etc. Although the parent pyrrolo[2,3-d]pyrimidine is known
to possess fluorescence properties10 and some derivatives were
demonstrated to be suitable for probing the structure of DNA,11
exploitation of this heteoaromatic core in functional p-systems is
insufficient. Only recently, we have found that pyrrolo[2,3-d]py-
rimidine-core based oligoarylenes possess interesting fluorescent
properties.12 To develop more efficient light-emitting materials we
2. Results and discussion
report herein on the sequential assembly of p-systems, such as aryl
As mentioned above, our synthetic strategy towards the target
compounds was based on a combination of the palladium-
catalyzed Suzuki cross-coupling reactions of 2,4-dichloropyrrolo
[2,3-d]pyrimidine16 (1) with arylboronic acids and copper-
catalyzed N-arylations of 7H-pyrrolo[2,3-d]pyrimidines with aryl
halides. Therefore, a set of seven phenylboronic acids (2aeg) and
four phenyl iodides and bromides (3aed) has been chosen (Fig. 1)
as the reagents for the particular arylations in different position.
groups, onto the pyrrolo[2,3-d]pyrimidine core as a useful method
for the construction of mono-, di- and triarylpyrrolo[2,3-d]pyrim-
idines bearing various aryl branches in positions 2, 4 and 7 of the
* Corresponding author. Tel.: þ370 610 06920; fax: þ370 5 2330987; e-mail
address: sigitas.tumkevicius@chf.vu.lt (S. Tumkevicius).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.10.040

330
J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
obtained in higher yields. However, all attempts to obtain 4-aryl-2-
chloro-7-tert-butoxycarbonylpyrrolo[2,3-d]pyrimidines by the re-
action of 6 with arylboronic acids 2 failed. In order to obtain 2,4-
diarylpyrrolopyrimidines with different aryl groups the second
Suzuki coupling of 4-aryl-2-chloropyrrolo[2,3-d]pyrimidines (4)
with arylboronic acids was investigated. But compounds 4 were
found to be inert to the selected arylboronic acids although various
catalyst systems were examined. The catalysts and ligands
employed were PdCl2(PPh3)2, PdCl2(dppf), Pd(OAc)2 and PCy2(2-
biphenyl), PCy2[20,60-(MeO)2-2-biphenyl], P(t-Bu)2(2-biphenyl),
P(i-Pr)2(2-biphenyl) and dppf, correspondingly. Otherwise, the
Suzuki coupling of the N(7)-Boc derivatives 8a,f, obtained by the
reaction of 4a,f with Boc2O in the presence of DMAP and DIPEA,
with the selected arylboronic acids furnished pyrrolopyrimidines
9e11 bearing different aryl groups in positions 2 and 4 of hetero-
cyclic moiety in good yields (Scheme 2, Table 1). The second Suzuki
coupling was accomplished by reflux of the reaction mixture in 1,4-
dioxane for 4e7 h in the presence of Pd(OAc)2/PCy2(2-biphenyl)/
K3PO4 as a catalyst system. Deprotection of N(7)-Boc group with
hydrochloric acid in acetone or TFA in dichloromethane afforded
the corresponding 2,4-diarylpyrrolopyrimidines 12e14.
t-Bu
N
B(OH)2
B(OH)2
B(OH)2
B(OH)2
B(OH)2
2e
2d
2a
2b
2c
OMe
OEt
OMe
CN
N
B(OH)2
I
B(OH)2
I
I
Br
3d
2f
2g
3a
3b
3c
Fig. 1. Set of arylboronic acids and aryl halides.
We have found that the Suzuki coupling of 2,4-dichloropyrrolo
[2,3-d]pyrimidine (1) with arylboronic acids 2 depending on the
amount of arylboronic acid and reaction conditions gives 4-aryl-2-
chloro- (4aef) or 2,4-diarylpyrrolo[2,3-d]pyrimidines (5aee), re-
spectively12 (Scheme 1).
R
R
i
N
N
N
Boc
N
H
Cl
N
Cl
N
4a,f
8a,f
ii
R
R
iii
N
N
N
H
N
Boc
N
N
R'
R'
12-14
9-11
Scheme 2. Reagents and conditions: (i) Boc2O, DMAP, DIPEA, CH2Cl2; (ii) 2 mol %
Pd(OAc)2, 4 mol % PCy2(2-biphenyl), 1.2 equiv ArB(OH)2, 2.4 equiv K3PO4, 1,4-dioxane,
D, Ar; (iii) HCl, Me2CO, D or TFA, DCM, rt.
Table 1
Preparation of compounds 8a,f and 9e14
Compd
R
R0
Yield, %
8a
8f
9
10
11
12
13
14
H
d
61
80
76
79
69
73
80
77
Scheme 1. Reagents and conditions: (i) 2 mol % Pd(OAc)2, 4 mol % PCy2(2-biphenyl),
1.2 equiv ArB(OH)2, 2.4 equiv K3PO4, 1,4-dioxane, 60e70 ꢀC, Ar; (ii) 2 mol % Pd(OAc)2,
4-MeO
H
H
4-MeO
H
H
d
4-Ph
4-EtO
4-EtO
4-Ph
4-EtO
4-EtO
4 mol % PCy2(2-biphenyl), 2.4 equiv ArB(OH)2, 4.8 equiv K3PO4, 1,4-dioxane,
Boc2O, DMAP, DIPEA, CH2Cl2; (iv) mol Pd(OAc)2, mol PCy2(2-biphenyl),
2.4 equiv ArB(OH)2, 4.8 equiv K3PO4, 1,4-dioxane, , Ar.
D, Ar; (iii)
2
%
4
%
D
4-MeO
Mono cross-coupling reaction of 1 with arylboronic acids 2 to
give compounds 4aef was accomplished at 60e70 ꢀC in 1,4-
dioxane using 1.2 equiv of the corresponding boronic acid and
Pd(OAc)2/PCy2(2-biphenyl)/K3PO4 as a catalyst system. Reflux of 1
with 2.4 equiv of 2 using the same catalytic system led to the cor-
responding 2,4-diarylpyrrolo[2,3-d]pyrimidines 5aee in moderate
yields. Low yield (29%) of 5d was obtained mainly because of the
formation in considerable amount of a side-productdp-quater-
phenyl. The presence of a N(7)-Boc group in 6 increased the re-
activity of the 2-chlorine group and compounds 7aef were
The obtained 5a, 5e and 12e14 were subjected to N-arylation
reaction (Scheme 3). CuI/(ꢁ)-trans-1,2-diaminocyclohexane/K3PO4
was used as a catalyst system of choice.17 Employing other ligands
and bases in the reaction gave worse results. For example, the re-
action of 5e with iodobenzene using CuI/(ꢁ)-trans-1,2-
diaminocyclohexane/K3PO4 as a catalyst system furnished 22 in
85% yield (Table 2, entry 8), while using in the reaction CuI/1,10-
phenanthroline/Cs2CO3 as
a catalyst system gave the target

J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
331
excellent (Table 2). Lower yields of compounds 23e25 (Table 2,
entries 9e11) were obtained, presumably because of more complex
their purification by column chromatography.
R
N
R
Taking into account that introduction of aryl groups by the
Suzuki coupling into position 2 of 4-arylpyrrolopyrimidines was
successful only when N(7)-protected derivatives were employed, it
was of interest to evaluate the possibility of the synthesis of 2,4,7-
triarylpyrrolo pyrimidines by an alternate and shorter route. This is
exemplified by the synthesis of compound 26 by N-arylation of 4f
with iodobenzene and following Suzuki coupling of the obtained 27
with boronic acid 2g (method B) (Scheme 4). Total conversion of 4f
in its N-arylation reaction with iodobenzene to give 27 was ach-
ieved after 33 h and using 12 mol % CuI and 30 mol % (ꢁ)-trans-
diaminocyclohexane. However, a complex mixture of products was
formed in the reaction and compound 27 was isolated only in 37%
yield.
The Suzuki coupling of 27 with 4-ethoxyphenylboronic acid
gave the desired 26 in 64% yield. It is worthy of note that the latter
reaction appeared to be much slower (20 h) than that of N(7)-Boc
derivative 8f with the same boronic acid (6 h). This supports our
observation in the synthesis of 7aef that Boc group increases the
reactivity of the chlorine group in the position 2 of pyrrolopyr-
imidine. Yield of compound 26 (24%) calculated for two reactions
(Scheme 4) was considerably lower than the yield of its synthesis
i
N
N
N
H
N
N
R'
R'
15-26
5a,e, 12-14
R''
Scheme 3. Reagents and conditions: (i) 4-R00C6H4-I(Br), CuI, (ꢁ)-trans-1,2-
diaminocyclohexane, K3PO4, 1,4-dioxane,
D, Ar.
compound 22 in 49% yield (experimental, method B). To achieve
full conversion of compounds 5a, 5e and 12e14 in the N-arylation
reaction an amount of CuI ranging from 3 mol % to 10 mol % was
used (Table 2). The reaction proceeded at reflux temperature of
dioxane and worked well with aryl iodides and bromides bearing
electron-donating or electron-withdrawing groups. It should be
noted that better results of N-arylation reaction were obtained
when the indicated amount of CuI was added to the reaction
mixture in portions during the reaction. The yields of 2,4,7-
triarylpyrrolo[2,3-d]pyrimidines (15e26) varied from good to
Table 2
Preparation of 2,4,7-triarylpyrrolo[2,3-d]pyrimidines (15e26)
Entry
Compd 5a,e or 12e14
Aryl halide 3aed
CuI, mol %
Reaction time, hr
Product 15e26
Yield, %
N
1
5a
3a
4
13
94
N
N
15
N
2
5a
3b
5
12
92
N
N
16
OMe
N
3
5a
3c
5
12
82
N
N
17
CN
N
N
N
4
5a
3d
6
22
72
18
N
(continued on next page)

Table 2 (continued )
Entry
Compd 5a,e or 12e14
Aryl halide 3aed
CuI, mol %
Reaction time, hr
Product 15e26
Yield, %
N
5
12
3b
5
11
93
N
N
19
OMe
N
6
12
3c
10
25
95
N
N
20
CN
N
7
13
3c
3
6
90
N
N
21
EtO
CN
N
8
5e
3a
5
10
85
51
57
N
N
N
N
22
N
9
5e
3b
7
19
N
N
N
N
23
OMe
N
10
5e
3c
7
22
N
N
N
N
24
CN

J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
333
Table 2 (continued )
Entry
Compd 5a,e or 12e14
Aryl halide 3aed
CuI, mol %
Reaction time, hr
Product 15e26
Yield, %
N
N
11
5e
3d
8
29
59
N
N
N
25
N
OMe
12
14
3a
5
9.5
99
N
N
N
26
EtO
Introduction of electron-donating methoxy and diphenylamino
groups (compounds 16, 18, 23, and 25) results in a significant red
shift of the spectral bands. This effect for methoxy group is about
32e33 nm, whereas for diphenylamino group it amounts to
112e116 nm (Table 3, compare entry 1 with entries 2, 4 and entry 8
with entries 9, 11).
OMe
OMe
OMe
ii
i
37%
64%
N
N
N
Conversely, cyano group in the para-position of N(7)-aryl groups
causes a blue shift of the fluorescence bands (Table 3, compare
entry 1 with entry 3). However, 7-(4-cyanophenyl)pyrrolopyr-
imidines 17, 20, 24 exhibit a slightly better fluorescence quantum
yield than corresponding 7-(4-methoxyphenyl) derivatives 16, 19,
23 (Table 3). Comparing the fluorescence quantum yields of pyr-
rolopyrimidines 15e26 with those obtained for corresponding
compounds 5aee12 it can be concluded that aryl groups in the
position 7 of pyrrolo[2,3-d]pyrimidine reduce fluorescence quan-
tum yield. Especially significant drop of fluorescence is observed for
compounds 18, 25 containing 4-(diphenylamino)phenyl group at
the nitrogen atom of the pyrrole ring (Table 3, entries 4, 11). Con-
sidering the fluorescence lifetimes estimated in THF solutions of
the studied compounds it is seen that most of them span the range
from 2.1 to 4.6 ns, which is typical for fluorescent organic molecules
featuring significant radiative probability. Exception is observed for
7-(4-methoxyphenyl)pyrrolopyrimidines 16, 19 and 23, which
demonstrate prolonged fluorescence decay times ranging from 10.4
to 12.2 ns (Table 3, entries 2, 5, 9).
N
N
N
H
N
Cl
N
Cl
N
EtO
4f
27
26
Scheme 4. Reagents and conditions: (i) PhI, CuI, (ꢁ)-trans-1,2-diaminocyclohexane,
K3PO4, 1,4-dioxane, , Ar; (ii) 2 mol % Pd(OAc)2, 4 mol % PCy2(2-biphenyl), 1.5 equiv 4-
EtOC6H4B(OH)2, 3.0 equiv K3PO4, 1,4-dioxane, , Ar.
D
D
using four reaction sequence (42%) including the N(7)-protection
and deprotection reactions (Schemes 2 and 3).
Optical properties of the synthesized 2,4-diaryl- and 2,4,7-
triarylpyrrolo[2,3-d]pyrimidines were assessed by performing ab-
sorption and fluorescence spectroscopy, fluorescence lifetime and
fluorescence quantum yield measurements. Photophysical proper-
ties of the compounds 5aee and 7aef in THF solutions are dis-
cussed in our preliminary communication.12 Absorption and
fluorescence data of 2,4,7-triarylpyrrolo[2,3-d]pyrimidines (15e26)
are summarized in Table 3. Triarylpyrrolopyrimidines 15e26 were
found to exhibit strong UV absorption in dilute THF solution with
their absorption maxima positioned below 342 nm. Aryl groups in
position 7 enhances the absorption of triarylpyrrolopyrimidines as
compared with the corresponding 2,4-diaryl derivatives.12 The
most prominent hyperchromic effect is observed for compounds
16, 18, 23, 25 containing electron-donating methoxy and diphe-
nylamino groups in the N(7)-aryl group (Table 3, entries 2, 4, 9, 11)
when compared with the corresponding data of compounds 5a,e.12
Depending on the origin of aryl branches of the compounds 15e26
their emission maxima are located in the range of 402e539 nm
with fluorescence quantum yields ranging from 2% to 40%. Sub-
stituents in the para-position of N(7)-aryl groups of the compounds
have a dramatic effect on a position of their fluorescence bands.
3. Conclusions
In summary, we have developed a simple synthetic strategy that
permits the assembly of aromatic p-systems onto a pyrrolo[2,3-d]
pyrimidine core in a programmable and diversity-oriented format.
The investigation of synthetic routes for the preparation of 2,4-
diaryl- and 2,4,7-triarylpyrrolo[2,3-d]pyrimidines bearing differ-
ent
aryl
branches
revealed
the
necessity
of
pro-
tectionedeprotection methodology of N(7)-position of pyrrolo[2,3-
d]pyrimidine. The vast majority of the synthesized 2,4-diaryl- and

334
J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
Table 3
the sample solutions were ensured to be below 0.05 to avoid
reabsorption effects. Estimated quantum yield was verified by us-
ing an alternative method of an integrating sphere (Sphere Op-
tics),19 which was coupled to the CCD spectrometer by an optical
fibre. Fluorescence transients of the sample solutions were mea-
sured using time-correlated single photon counting system (Pico-
Quant PicoHarp 300). IR spectra were run on a PerkineElmer FT-IR
spectrophotometer Spectrum BX II in KBr. 1H and 13C NMR spectra
were recorded on a Varian INOVA spectrometer (300 MHz and
75 MHz, respectively). HRMS spectra were obtained on a mass
spectrometer Dual-ESI Q-TOF 6520 (Agilent Technologies). Column
chromatography was performed using Silica gel 60
(0.040e0.063 mm) (Merck). All reactions and purity of the syn-
thesized compounds were monitored by TLC using Silica gel 60 F254
aluminium plates (Merck). Visualization was accomplished by UV
light. Physical and spectral characteristics of compounds 4b, 4d, 5b,
5d, 5e, 6 and 7b, 7e, 7f are presented in our preliminary
communication.12
UV absorption and PL data of 2,4,7-triarylpyrrolo-[2,3-d]pyrimidines (15e26) in
10ꢃ5 THF solution
Entry
1
Compd
labs, nm
3
, l molꢃ1 cmꢃ1
lem
,
a nm
FF, %
s b
4.6
,
ns
15
256
327
210
259
341
210
265
292
326
210
267
308
242
260
297
344
280
332
235
275
324
210
236
254
281
292
342
210
237
255
292
342
210
236
256
284
291
342
237
255
293
341
291
330
42,432
10,759
116,315
100,284
20,855
51,091
54,001
26,948
15,588
80,942
41,473
39,999
13,928
17,523
20,932
7897
416
30
2
3
16
17
448
21
23
12.2
2.6
403
4
5
18
19
528
449
4
6.5
30
10.6
6
7
20
21
28,639
13,226
10,753
27,097
9602
402
408
34
23
2.33
2.14
3.7
4.1.1. 2-Chloro-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (4a). A solu-
tion of compound 1 (0.5 g, 2.66 mmol) in anhydrous dioxane
(10 mL) was flushed with argon and 2.0 mol % Pd(OAc)2 and
4.0 mol % (2-biphenyl)dicyclohexylphosphine were added under
stirring and argon flow. After 10 min phenylboronic acid (2a)
(0.39 g, 3.20 mmol) and K3PO4 (1.35 g, 6.37 mmol) was added. The
reaction mixture was stirred at 60e70 ꢀC (bath temperature) for
4 h. Then dioxane was evaporated under reduced pressure to dry-
ness and water (5 mL) was added to dissolve inorganic salts. The
obtained solution was extracted with chloroform (3ꢂ25 mL), or-
ganic layer dried with Na2SO4, chloroform removed by distillation
under reduced pressure and the solid obtained was purified by
column chromatography using chloroform as an eluent to give
compound 4a (0.27 g, 45%) as a yellowish solid, mp 210 ꢀC. [Found:
C, 63.02; H, 3.71. C12H8ClN3 requires C, 62.76; H, 3.51%]; nmax
3449 cmꢃ1 (NH); dH (CDCl3): 6.92 (1H, dd, J3¼3.6 Hz, J4¼2.1 Hz, 5-
H), 7.47 (1H, dd, J3¼3.6 Hz, J3¼2.1 Hz, 6-H), 7.59e7.63 (3H, m, 30-50-
H), 8.18e8.21 (2H, m, 20,60-H), 10.69 (1H, s, NH); dC (DMSO-d6):
101.2, 114.5, 129.4, 129.7, 129.8, 131.4, 137.3, 152.8, 154.9, 158.2.
8
22
83,354
95,604
73,364
40,217
40,074
40,627
80,911
97,694
71,874
44,901
41,076
121,627
99,333
76,639
54,569
53,153
41,433
115,282
75,367
62,155
63,694
20,441
7079
423
36
9
23
24
456
438
20
40
10.4
10
3.9
11
25
26
539
403
2
3.8
12
31
2.39
4.1.2. 4-[4-(9-Carbazolyl)phenyl]-2-chloro-7H-pyrrolo[2,3-d]pyrimi-
dine (4e). Compound 4e was synthesized and isolated according to
the procedure described for the preparation of compound 4a. The
reaction time 2.5 h. Yield 47%, yellow solid, mp 309.6e309.8 ꢀC.
[Found: C, 73.39; H, 4.02. C24H15ClN4 requires C, 73.00; H, 3.83%]; dH
(CDCl3): 7.01 (1H, dd, J3¼3.6 Hz, J4¼2.1 Hz, 5-H), 7.34e7.39 (2H, m,
30,50-H), 7.46e7.58 [5H, m, 200,300,600,700-H (carbazolyl), 6-H], 7.84
[2H, dm, J¼8.7 Hz, 100,800-H (carbazolyl)], 8.21 [2H, dm, J¼7.5 Hz,
400,500-H (carbazolyl)], 8.44 (2H, dm, J¼9 Hz, 20,60-H), 9.49 (1H, s,
NH); dC (DMSO-d6): 101.3, 110.5, 114.4, 121.2, 121.4, 123.8, 127.1,
127.5, 129.8, 131.3, 135.9, 139.7, 140.4, 152.9, 154.9, 157.3.
a
Excited at 340 nm.
Fluorescence lifetime estimated at lem
b
.
2,4,7-triarylpyrrolo[2,3-d]pyrimidines exhibit near UV-blue fluo-
rescence with emission maxima in THF solution ranging from
380 nm to 460 nm. A more detailed study of the photophysical
properties of the synthesized compounds in various solvents and in
the solid state and further variations of oligoarylene branches at the
pyrrolo[2,3-d]pyrimidine are currently in progress and the results
will be reported in due course.
4. Experimental section
4.1. General
4.1.3. 2-Chloro-4-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine
(4f). Compound 4f was synthesized and isolated according to the
procedure described for the preparation of compound 4a. The re-
action time 3.5 h. Yield 51%, yellow solid, mp 249e249.6 ꢀC. dH
(CDCl3): 3.94 (3H, s, CH3O), 6.91 (1H, dd, J3¼3.8 Hz, J4¼2.1 Hz, 5-H),
7.11 (2H, dm, J¼9 Hz, 30,50-H), 7.42 (1H, dd, J3¼3.9 Hz, J3¼2.4 Hz, 6-
H), 8.19 (2H, dm, J¼8.7 Hz, 20,60-H), 9.99 (1H, s, NH); dC (DMSO-d6):
56.1, 101.4, 115.1, 128.9, 129.6, 131.1, 132.4, 152.9, 154.6, 157.9, 162.1;
HRMS (ESI): MHþ, found 260.0587. C13H10ClN3O requires 260.0585.
Melting points were determined in open capillaries with a dig-
ital melting point IA9100 series apparatus (ThermoFischer Scien-
tific) and are uncorrected. The absorption spectra were recorded on
a PerkineElmer UVevis spectrophotometer Lambda 20 in THF so-
lutions. Fluorescence of the sample solutions was excited by
340 nm wavelength light-emitting diode and measured using back-
thinned CCD spectrometer (Hamamatsu PMA-11). The fluorescence
quantum yield of the solutions was estimated by comparing
wavelength-integrated fluorescence intensity of the solution with
that of the reference. Quinine sulfate dissolved in 0.1 M H2SO4 has
been used as a reference.18 Optical densities of the reference and
4.1.4. 2,4-Diphenyl-7H-pyrrolo[2,3-d]pyrimidine (5a). A solution of
compound 1 (0.3 g, 1.60 mmol) in anhydrous dioxane (10 mL) was
flushed with argon and 2.0 mol % Pd(OAc)2 and 4.0 mol % (2-
biphenyl)dicyclohexylphosphine were added under stirring and
argon flow. After 10 min phenylboronic acid (2a) (0.47 g,

J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
335
3.83 mmol) and K3PO4 (1.62 g, 7.66 mmol) were added. The re-
action mixture was stirred under reflux for 4 h. Then dioxane was
evaporated under reduced pressure to dryness and water (5 mL)
was added to dissolve inorganic salts. The obtained solution was
extracted with chloroform (3ꢂ25 mL), organic layer was dried with
Na2SO4, chloroform removed by distillation under reduced pres-
sure and the solid was purified by column chromatography using
benzene as an eluent to give compound 5a (0.28 g, 65%) as a yel-
lowish solid, mp 210 ꢀC. [Found: C, 79.47; H, 4.95. C18H13N3 requires
141.6, 141.7, 142.2, 148.8, 156.0, 157.8, 158.3; HRMS (ESI): MHþ,
found 524.2327. C35H29N3O2 requires 524.2333.
4.1.8. tert-Butyl 2,4-di(biphenyl-4-yl)-7H-pyrrolo[2,3-d]pyrimidine-
7-carboxylate (7d). Compound 7d was synthesized and isolated
according to the procedure described for the preparation of com-
pound 7a. The reaction time 2 h. Yield 66%, yellowish solid, mp
165e165.4 ꢀC (from 2-propanol). [Found: C, 80.14; H, 5.56.
C35H29N3O2 requires C, 80.28; H, 5.58%]; dH (CDCl3): 1.85 (9H, s, tert-
Boc), 6.98 (1H, d, J¼4.2 Hz, 5-H), 7.41e7.89 [15H, m, 6-H, 30,50,200-600-
H (2-biPh, 4-biPh)], 8.34 [2H, dm, J¼8.1 Hz, 20,60-H (4-biPh)], 8.84
[2H, dm, J¼8.4 Hz, 20,60-H (2-biPh)]; dC (CDCl3): 28.5, 85.2, 104.5,
116.5, 127.3, 127.4, 127.4, 127.5, 127.7, 127.8, 128.1, 129.0, 129.1, 129.2,
129.8, 137.2, 137.8, 140.7, 141.1, 142.9, 143.3, 148.6, 154.2, 157.9, 159.7.
C, 79.68; H, 4.83%]; nmax 3435 cmꢃ1 (NH); UV (THF), lmax
( 3 ,
l molꢃ1 cmꢃ1): 216 (3ꢂ104), 264 (4ꢂ104), 316 (1ꢂ104); dH (CDCl3):
6.94 (1H, dd, J3¼3.75 Hz, J4¼1.8 Hz, 5-H), 7.39 (1H, dd, J3¼3.6 Hz,
J3¼2.4 Hz, 6-H), 7.55e7.64 [6H, m, 30,40,50-H (2-Ph, 4-Ph)], 8.34 [2H,
dm, J¼9.6 Hz, 20,60-H (4-Ph)], 8.64 [2H, dm, J¼9.9 Hz, 20,60-H (2-
Ph)], 10.05 (1H, s, NH); dC (DMSO-d6): 100.9; 113.9; 128.2; 128.9;
129.3; 129.4; 129.6; 130.3; 130.8; 138.9; 139.3; 154.4; 156.2; 156.9.
4.1.9. tert-Butyl 2-chloro-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine-7-
carboxylate (8a). To
a solution of compound 4a (0.42 g,
4.1.5. 2,4-Di(biphenyl-3-yl)-7H-pyrrolo[2,3-d]pyrimidine
(5c). Compound 5c was synthesized and isolated according to the
procedure described for the preparation of compound 5a. The re-
action time 2.5 h. Eluent for column chromatographydchloroform.
Yield 49%, yellowish solid, mp 226e227 ꢀC. nmax 3028 cmꢃ1 (NH);
1.83 mmol) in anhydrous dichloromethane (5 mL) DIPEA (0.48 mL,
2.75 mmol), DMAP (0.07 g, 0.57 mmol) and Boc2O (0.6 g,
2.75 mmol) were added. The reaction mixture was stirred under
reflux for 1 h 20 min. Then dichloromethane was evaporated, the
obtained residue was purified by column chromatography using
chloroform as an eluent to give compound 8a (0.37 g, 61%) as
a colourless solid, mp 76e77 ꢀC (from 2-propanol). dH (CDCl3): 1.74
(9H, s, tert-Boc), 6.89 (1H, d, J¼4.2 Hz, 5-H), 7.58e7.61 (3H, m,
30,40,50-H), 7.74 (1H, d, J¼4.2 Hz, 6-H), 8.06e8.09 (2H, m, 20,60-H); dC
(CDCl3): 28.3, 86.0, 104.1, 116.9, 128.0, 129.2, 129.3, 131.2, 136.6,
147.3, 154.4, 156.2, 160.6; HRMS (ESI): MHþ, found 330.1000.
C17H16ClN3O2 requires 330.1004.
UV (THF), lmax
(
3
, l molꢃ1 cmꢃ1): 215 (4ꢂ104), 258 (7ꢂ104), 325 nm
(1ꢂ104); dH (CDCl3): 6.96 (1H, dd, J3¼3.6 Hz, J4¼1.8 Hz, 5eH),
7.36e7.81 [15H, m, 6-H, 40,50,200-600-H (2-biPh), 30,40,200-600-H (4-
biPh)], 8.29e8.32 [1H, m, 20-H (4-biPh)], 8.55e8.56 [1H, m, 20-H
(2-biPh)], 8.62e8.65 [1H, m, 60-H (4-biPh)], 8.90e8.91 [1H, m, 60-H
(2-biPh)], 9.80 (1H, s, NH); dC (DMSO-d6): 101.0, 114.2, 126.4, 127.2,
127.3, 127.4, 127.5, 127.6, 128.4, 128.5, 128.7, 129.0, 129.3, 129.8,
129.9, 130.0, 130.4; HRMS (ESI): MHþ, found 424.1800. C30H21N3
requires 424.1808.
4.1.10. tert-Butyl 2-chloro-4-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]
pyrimidine-7-carboxylate (8f). To a solution of compound 4f (0.18 g,
0.69 mmol) in anhydrous dichloromethane (5 mL) DIPEA (0.14 mL,
0.83 mmol), DMAP (0.017 g, 0.14 mmol) and Boc2O (0.23 g,
1.04 mmol) were added. The reaction mixture was stirred at room
temperature for 0.5 h. Then dichloromethane was evaporated, the
obtained residue was purified by column chromatography using
chloroform as an eluent to give compound 8f (0.20 g, 80%) as
a colourless solid, mp 170.3e170.8 ꢀC (from 2-propanol). dH (CDCl3):
1.73 (9H, s, tert-Boc), 3.94 (3H, s, OMe), 6.88 (1H, d, J¼4.2 Hz, 5-H),
7.09 (2H, dm, J¼9 Hz, 30,50-H), 7.71 (1H, d, J¼4.2 Hz, 6-H), 8.09 (2H,
dm, J¼9 Hz, 20,60-H); dC (CDCl3): 28.3, 55.7, 85.9, 104.2, 114.6, 116.2,
127.6, 129.1, 130.9, 147.3, 154.4, 156.1, 160.1, 162.2; HRMS (ESI): MHþ,
found 360.1112. C18H18ClN3O3 requires 360.1109.
4.1.6. tert-Butyl 2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimidine-7-
carboxylate (7a). A solution of compound 6 (0.1 g, 0.35 mmol) in
anhydrous dioxane (10 mL) was flushed with argon and 2.0 mol %
Pd(OAc)2 and 4.0 mol % (2-biphenyl)dicyclohexylphosphine were
added under stirring and argon flow. After 10 min phenylboronic
acid (0.10 g, 0.83 mmol) and K3PO4 (0.35 g, 1.67 mmol) were added.
The reaction mixture was stirred under reflux for 3.5 h. Then di-
oxane was evaporated under reduced pressure to dryness and
water (5 mL) was added to dissolve inorganic salts. The obtained
solution was extracted with chloroform (3ꢂ25 mL), organic layer
was dried with Na2SO4, chloroform removed by distillation under
reduced pressure and residue was purified by column chromatog-
raphy using chloroform as an eluent to give compound 7a (0.10 g,
78%) as a colourless solid, mp 121e122.4 ꢀC (from 2-propanol). UV
4.1.11. tert-Butyl 2-(biphenyl-4-yl)-4-phenyl-7H-pyrrolo[2,3-d]py-
rimidine-7-carboxylate (9). A solution of compound 8a (0.14 g,
0.42 mmol) in an anhydrous dioxane (10 mL) was flushed with
argon and 2.0 mol % Pd(OAc)2 and 4.0 mol % (2-biphenyl)dicyclo-
hexylphosphine were added under stirring and argon flow. After
10 min. 4-biphenylboronic acid (0.10 g, 0.51 mmol) and K3PO4
(0.22 g, 1.02 mmol) were added. The reaction mixture was stirred
under reflux for 7 h. Then dioxane was evaporated under reduced
pressure to dryness and water (5 mL) was added to dissolve in-
organic salts. The obtained solution was extracted with chloroform
(3ꢂ25 mL), organic layer was dried with Na2SO4, chloroform re-
moved by distillation under reduced pressure, the residue was
dissolved in a minimal amount of tetrachloromethane and purified
by column chromatography using hexane/ethyl acetate (27:1) as an
eluent to give compound 9 (0.145 g, 76%) as a colourless solid, mp
150e150.2 ꢀC (from 2-propanol). dH (CDCl3): 1.83 (9H, s, tert-Boc),
6.94 (1H, d, J¼4.2 Hz, 5-H), 7.49e7.79 [10H, m, 30,50,200-600-H (4-
biPh), 30,40,50-H (Ph)], 7.81 (1H, d, J¼3.9 Hz, 6-H), 8.22e8.25 [2H,
m, 20,60-H (Ph)], 8.80 [2H, dm, J¼8.7 Hz, 20,60-H (4-biPh)]; dC
(CDCl3): 28.5, 85.2, 104.5, 116.5, 127.4, 127.5, 127.6, 127.8, 129.0,
129.1, 129.2, 129.3, 130.5, 137.8, 138.3, 141.1, 142.9, 148.6, 154.2,
(THF), lmax
(
3
, l molꢃ1 cmꢃ1): 213 (4ꢂ104), 263 (4ꢂ104), 303
(2ꢂ104); dH (CDCl3): 1.81 (9H, s, tert-Boc), 6.93 (1H, d, J¼4.2 Hz, 5-
H), 7.52e7.63 [6H, m, 30,40,50-H (2-Ph, 4-Ph)], 7.81 (1H, d, J¼4.2 Hz,
6-H), 8.22 [2H, dm, J¼5.4 Hz, 20,60-H (4-Ph)], 8.73 [2H, dm, J¼6.6 Hz,
20,60-H (2-Ph)]; dC (DMSO-d6): 28.5, 85.1, 104.4, 116.5, 127.6, 128.6,
128.7, 129.1, 129.3, 130.4, 130.5, 138.3, 138.8, 148.6, 154.2, 158.3,
159.9.
4.1.7. tert-Butyl 2,4-di(biphenyl-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-
7-carboxylate (7c). Compound 7c was synthesized and isolated
according to the procedure described for the preparation of com-
pound 7a. The reaction time 3 h. Yield 42%, colourless solid, mp
139e139.6 ꢀC (from 2-propanol). UV (THF),
l
, nm (
, l molꢃ1 cmꢃ1):
3
256 (6ꢂ104), 305 (2ꢂ104); dH (CDCl3): 1.82 (9H, s, tert-Boc), 6.97
(1H, d, J¼4.2 Hz, 5-H), 7.39e7.81 [14H, m, 40,50,200-600-H (2-biPh, 4-
biPh)], 7.85 (1H, d, J¼4.2 Hz, 6-H), 8.20 [1H, dm, J¼7.5 Hz, 60-H
(4-biPh)], 8.44 [1H, t, J¼1.8 Hz, 20-H (4-biPh)], 8.75 [1H, dm,
J¼7.8 Hz, 60-H (2-biPh)], 8.99 [1H, t, J¼1.8 Hz, 20-H (2-biPh)]; dC
(CDCl3): 28.5, 85.3, 104.4,116.8,127.4,127.5,127.6,127.7,127.8,127.9,
128.1, 128.2, 128.9, 129.2, 129.25, 129.3, 129.6, 138.8, 139.2, 141.1,

336
J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
158.3, 159.7; HRMS (ESI): MHþ, found 448.2013. C29H25N3O2 re-
quires 448.2020.
(DMSO-d6): 1.39 (3H, t, J¼6.9 Hz, Me), 3.89 (3H, s, OMe), 4.12 (2H, q,
J¼6.9 Hz, OCH2), 6.89 (1H, dd, J3¼3.6 Hz, J4¼1.5 Hz, 5-H), 7.08 [2H,
dm, J¼9 Hz, 30,50-H (EtOPh)], 7.18 [2H, dm, J¼8.7 Hz, 30,50-H
(MeOPh)], 7.60 (1H, dd, J3¼3.5 Hz, J3¼2.1 Hz, 6-H), 8.32 [2H, dm,
J¼8.7 Hz, 20,60-H (MeOPh)], 8.48 [2H, dm, J¼9 Hz, 20,60-H (EtOPh)],
12.16 (s, 1H, NH); dC (DMSO-d6): 15.4, 56.1, 63.8, 101.0, 112.7, 114.9,
127.9, 129.6, 130.9, 131.4, 131.8, 154.4, 155.7, 156.9, 160.6, 161.6;
HRMS (ESI): MHþ, found 346.1546. C21H19N3O2 requires 346.1550.
4.1.12. tert-Butyl 2-(4-ethoxyphenyl)-4-phenyl-7H-pyrrolo[2,3-d]py-
rimidine-7-carboxylate (10). Compound 10 was synthesized and
isolated according to the procedure described for the preparation of
compound 9. Eluent for column chromatographydchloroform. The
reaction time 4 h. Yield 79%, yellowish solid, mp 141e141.9 ꢀC (from
2-propanol). dH (CDCl3): 1.49 (3H, t, J¼6.9 Hz, Me), 1.81 (9H, s, tert-
Boc), 4.16 (2H, q, J¼6.9 Hz, CH2O), 6.88 (1H, d, J¼4.2 Hz, 5-H), 7.05
[2H, dm, J¼9 Hz, 30,50-H (EtOC6H4)], 7.58e7.61 [3H, m, 30,40,50-H
(Ph)], 7.75 (1H, d, J¼4.2 Hz, 6-H), 8.19e8.22 [2H, m, 20,60-H (Ph)],
8.68 [2H, dm, J¼9 Hz, 20,60-H (EtOC6H4)]; dC (CDCl3): 15.1, 28.5, 63.7,
84.9, 104.4, 114.5, 115.9, 127.1, 129.0, 129.3, 130.1, 130.4, 131.4, 138.4,
148.6, 154.3, 158.2, 159.9, 161.1; HRMS (ESI): MHþ, found 416.1962.
C25H25N3O3 requires 416.1969.
4.1.17. 2,4,7-Triphenyl-7H-pyrrolo[2,3-d]pyrimidine (15). A solution
of compound 5a (0.15 g, 0.55 mmol) in anhydrous dioxane (3 mL)
was flushed with argon and 1.0 mol % CuI, anhydrous K3PO4 (0.21 g,
0.99 mmol), iodobenzene (0.052 mL, 0.46 mmol), 10.0 mol %
(ꢁ)-trans-1,2-diaminocyclohexane were added under stirring and
argon flow. The reaction mixture was stirred under reflux for 6 h
and 1.0 mol % of CuI was added. Then every 2 h 1.0 mol % of CuI was
added to the mixture till the total amount of CuI reached 4.0 mol %.
Total reaction time was 13 h. Then after cooling to room tempera-
ture ethyl acetate (5 mL) was added to the reaction mixture and
resulting solution was filtered through a layer of silica gel eluting
with ethyl acetate. The filtrate was concentrated under reduced
pressure, the residue was dissolved in a minimal amount of tetra-
chloromethane and purified by column chromatography using
hexane/ethyl acetate (40:1) as an eluent to give compound 15
4.1.13. tert-Butyl 2-(4-ethoxyphenyl)-4-(4-methoxyphenyl)-7H-pyr-
rolo[2,3-d]pyrimidine-7-carboxylate (11). Compound 11 was syn-
thesized and isolated according to the procedure described for the
preparation of compound 9. Eluent for column chromatogra-
phydchloroform. The reaction timed6 h. Yield 69%, colourless
solid, mp 145e145.5 ꢀC (from 2-propanol). dH (CDCl3): 1.49 (3H, t,
J¼7.2 Hz, Me), 1.79 (9H, s, tert-Boc), 3.95 (3H, s, OCH3), 4.16 (2H, q,
J¼6.9 Hz, CH2O), 6.88 (1H, d, J¼3.9 Hz, 5-H), 7.03 [2H, dm, J¼9 Hz,
30,50-H (EtOC6H4)], 7.13 [2H, dm, J¼8.7 Hz, 30,50-H (MeOC6H4)], 7.73
(1H, d, J¼4.2 Hz, 6-H), 8.20 [2H, dm, J¼9 Hz, 20,60-H (MeOC6H4)],
8.66 [2H, dm, J¼9 Hz, 20,60-H (EtOC6H4)]; dC (CDCl3): 15.1, 28.5, 55.7,
63.7, 84.9, 104.5, 114.4, 114.5, 115.3, 126.8, 130.1, 130.8, 131.0, 131.5,
148.6, 154.3, 157.7, 159.8, 161.0, 161.6; HRMS (ESI): MHþ, found
446.2066. C26H27N3O4 requires 446.2074.
(0.15 g, 94%) as a colourless solid, mp 155.2e155.8 ꢀC. UV (THF),
l,
nm (
3
, l molꢃ1 cmꢃ1): 256 (4ꢂ104), 327 (1ꢂ104); dH (CDCl3): 7.04
(1H, d, J¼3.9 Hz, 5-H), 7.41e7.68 [10H, m, 6-H, 30-50-H (2-Ph, 4-Ph,
N7ePh)], 7.97e7.94 [2H, m, 20,60-H (N7ePh)], 8.29e8.34 [2H, m,
20,60-H (4-Ph)], 8.67e8.71 [2H, m, 20,60-H (2-Ph)]; dC (CDCl3): 102.5,
115.2, 124.1, 126.9, 128.4, 128.6, 128.8, 128.9, 129.3, 129.6, 129.9,
130.3, 138.1, 138.9, 139.1, 152.9, 158.0, 158.6; HRMS (ESI): MHþ,
found 348.1489. C24H17N3 requires 348.1495.
4.1.14. 2-(Biphenyl-4-yl)-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine
(12). To a solution of compound 9 (0.145 g, 0.32 mmol) in a mixture
of acetone (15 mL) and water (5 mL) concd hydrochloric acid
(0.08 mL, 0.97 mmol) was added. The reaction mixture was stirred
under reflux for 70 h, then cooled to room temperature, the pre-
cipitate was filtered off to give compound 12 (0.08 g, 73%) as
a colourless solid, mp 278.2e278.9 ꢀC. dH (DMSO-d6): 6.95 (1H, dd,
J3¼3.3 Hz, J4¼1.5 Hz, 5-H), 7.54e7.89 [11H, m, 6-H, 30,50,200-600-H
(biPh), 30-50-H (Ph)], 8.34e8.36 [2H, m, 20,60-H (Ph)], 8.66 [2H, dm,
J¼8.4 Hz, 20,60-H (biPh)], 12.36 (1H, s, NH); dC (DMSO-d6): 101.0,
113.9, 127.4, 127.5, 128.5, 128.8, 129.0, 129.4, 129.6, 129.8, 130.9,
138.4, 138.9, 140.4, 141.9, 154.4, 156.2, 156.7; HRMS (ESI): MHþ,
found 348.1493. C24H17N3 requires 348.1495.
4.1.18. 7-(4-Methoxyphenyl)-2,4-diphenyl-7H-pyrrolo[2,3-d]pyrimi-
dine (16). Compound 16 was synthesized according to the pro-
cedure described for compound 15. The reaction timed12 h.
Addition of CuI in an amount 1.0 mol % was started after 4 h of
reflux and repeated every 2 h till the total amount CuI reached
5.0 mol %. The isolation and purification was carried out analo-
gously 15 by column chromatography using hexane/ethyl acetate
(20:1) as an eluent to give compound 16 (92%) as a colourless solid,
mp 184.9e185.4 ꢀC. UV (THF),
l, nm (
3
, l molꢃ1 cmꢃ1): 210 (12ꢂ104),
259 (10ꢂ104), 341 (2ꢂ104); dH (CDCl3): 3.95 (3H, s, CH3O), 7.01 (d,
1H, J¼3.9 Hz, 5-H), 7.13e7.16 (m, 2H, N7-(4-MeOePh): 30,50-H),
7.49e7.64 (m, 7H, 6-H, 2-Ph, 4-Ph: 30-50-H), 7.79e7.83 (m, 2H, N7-
(4-MeOePh): 20,60-H), 8.31e8.35 (m, 2H, 4-Ph: 20,60-H), 8.66e8.69
(m, 2H, 2-Ph: 20,60-H); dC (CDCl3): 55.9, 101.9, 114.8, 114.9, 125.5,
128.4, 128.6, 128.9, 129.2, 129.3, 129.9, 130.2, 131.2, 139.0, 139.2,
152.9, 157.9, 158.5, 158.6; HRMS (ESI): MHþ, found 378.1598.
C25H19N3O requires 378.1601.
4.1.15. 2-(4-Ethoxyphenyl)-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine
(13). Compound 13 was synthesized and isolated according to the
procedure described for the preparation of compound 12. The re-
action timed7 days. Yield 80%, colourless solid, mp 275e276 ꢀC. dH
(DMSO-d6): 1.39 (3H, t, J¼6.9 Hz, Me), 4.13 (2H, q, J¼6.9 Hz, OCH2),
6.90 (1H, dd, J3¼3.5 Hz, J4¼1.8 Hz, 5-H), 7.08 [2H, dm, J¼9.0 Hz,
30,50-H (EtOPh)], 7.59e7.65 [4H, m, 6-H, 30-50-H (Ph)], 8.31 [2H, dm,
J¼7.9 Hz, 20,60-H (Ph)], 8.49 [2H, dm, J¼9.0 Hz, 20,60-H (EtOPh)],
12.21 (1H, s, NH); dC (DMSO-d6): 15.4, 63.9, 100.9,113.4, 114.9,128.4,
129.3, 129.6, 129.7, 130.8, 131.7, 138.9, 154.5, 156.1, 157.0, 160.6;
HRMS (ESI): MHþ, found 316.1446. C20H17N3O requires 316.1444.
4.1.19. 4-(2,4-Diphenyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)benzoni-
trile (17). Compound 17 was synthesized according to the pro-
cedure described for compound 15. The reaction timed12 h.
Addition of CuI in an amount 1.0 mol % was started after 2 h of
reflux and repeated every 2 h till the total amount CuI reached
5.0 mol %. The isolation and purification was carried out analo-
gously 15 by column chromatography using benzene as an eluent to
give compound 17 (82%) as a yellowish solid, mp 209e210 ꢀC. IR
4.1.16. 2-(4-Ethoxyphenyl)-4-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]
pyrimidine (14). To a solution of compound 11 (0.17 g, 0.38 mmol)
in an anhydrous dichloromethane (10 mL) TFA (6.3 mL) was added.
The reaction mixture was stirred at room temperature for 5 min.
Then dichloromethane and TFA were evaporated under reduced
pressure to dryness and the obtained residue was purified by col-
umn chromatography using chloroform as an eluent to give com-
pound 14 (0.10 g, 77%) as a yellowish solid, mp 225.3e226.3 ꢀC. dH
(KBr): 2227 (CN); UV (THF),
l
, nm (
3
, l molꢃ1 cmꢃ1): 210 (5ꢂ104),
265 (5ꢂ104), 292 (3ꢂ104), 326 (2ꢂ104); dH (CDCl3): 7.11 (1H, d,
J¼3.6 Hz, 5-H), 7.51e7.66 [7H, m, 6-H, 30-50-H (2-Ph, 4-Ph)],
7.92e7.95 [2H, m, 20,60-H (N7ePh)], 8.19e8.22 [2H, m, 30,50-H
(N7ePh)], 8.29e8.32 [2H, m, 20,60-H (4-Ph)], 8.66e8.69 [2H, m,
20,60-H (2-Ph)]; dC (CDCl3): 104.2, 109.9, 115.5, 118.7, 123.6, 127.4,
128.4, 128.7, 129.1, 129.3, 130.4, 130.6, 133.7, 138.5, 138.6, 141.7,

J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
337
153.3, 158.6, 159.1; HRMS (ESI): MHþ, found 373.1446. C25H16N4
requires 373.1448.
129.8, 131.3, 132.3, 134.4, 137.6, 138.1, 140.3, 142.4, 153.2, 157.6, 157.7,
167.7; HRMS (ESI): MHþ, found 449.1758. C31H20N4 requires
449.1761.
4.1.20. 4-(2,4-Diphenyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-N,N-di-
phenylaniline (18). Compound 18 was synthesized according to the
procedure described for compound 15. The reaction timed22 h.
Addition of CuI in an amount 1.0 mol % was started after 2 h of
reflux and repeated every 2 h till the total amount CuI reached
6.0 mol %. The isolation and purification was carried out analo-
gously 15 by column chromatography using hexane/ethyl acetate
(27:1) as an eluent to give compound 18 (72%) as a yellowish solid,
4.1.23. 4-[2-(4-Ethoxyphenyl)-4-phenyl-7H-pyrrolo[2,3-d]pyr-
imidin-7-yl]benzonitrile (21). Compound 21 was synthesized
according to the procedure described for compound 15. The re-
action timed6 h. Addition of CuI in an amount 1.0 mol % was
started after 1 h of reflux and repeated after 2 h till the total amount
CuI reached 3.0 mol %. The isolation and purification was carried
out analogously 15 by column chromatography using hexane/ethyl
acetate (27:1) as an eluent to give compound 21 (90%) as a colour-
mp 166e166.2 ꢀC. UV (THF),
l, nm (
3
, l molꢃ1 cmꢃ1): 210 (8ꢂ104),
267 (4ꢂ104), 308 (4ꢂ104); dH (CDCl3): 7.02 (1H, d, J¼3.6 Hz, 5-H),
7.08e7.18 [2H, m, 30,50-H (N7ePh)], 7.23e7.39 [10H, m, 2ꢂ200-600-H
(N(Ph)2)], 7.48e7.68 [7H, m, 6-H, 30-50-H (2-Ph, 4-Ph)], 7.80e7.83
[2H, m, 20,60-H (N7ePh)], 8.32e8.35 [2H, m, 20,60-H (4-Ph)],
8.68e8.71 [2H, m, 20,60-H (2-Ph)]; dC (CDCl3): 102.2, 115.2, 123.5,
124.4, 124.7, 124.8, 128.4, 128.7, 128.9, 129.0, 129.3, 129.7, 129.9,
130.3, 132.5, 138.9, 139.1, 146.7, 147.9, 152.8, 157.9, 158.6; HRMS
(ESI): MHþ, found 515.2225. C36H26N4 requires 515.2230.
less solid, mp 206.3e206.8 ꢀC (from 2-PrOH/EtOAc). UV (THF),
l,
nm (
3
, l molꢃ1 cmꢃ1): 235 (1ꢂ104), 275 (3ꢂ104), 324 (1ꢂ104); dH
(CDCl3): 1.51 (3H, t, J¼6.9 Hz, Me), 4.17 (2H, q, J¼6.9 Hz, OCH2),
7.04e7.09 [3H, m, 5-H, 30,50-H (4-EtOC6H4)], 7.61e7.62 [4H, m, 6-H,
30,40,50-H (Ph)], 7.93 [2H, dm, J¼9.0 Hz, 30,50-H (N7ePh)], 8.21 [2H,
dm, J¼9.0 Hz, 20,60-H (N7ePh)], 8.30 [2H, m, J¼7.9 Hz, 20,60-H (Ph)],
8.1 [2H, dm, J¼9.0 Hz, 20,60-H (4-EtOC6H4)]; dC (CDCl3): 15.1, 63.8,
104.2, 109.7, 114.6, 114.9, 118.8, 123.6, 126.9, 129.1, 129.3, 129.9,
130.5, 131.1, 133.7, 138.5, 141.8, 153.3, 158.5, 159.1, 161.1; HRMS (ESI):
MHþ, found 417.1710. C27H20N4O requires 417.1710.
4.1.21. 2-(Biphenyl-4-yl)-7-(4-methoxyphenyl)-4-phenyl-7H-pyrrolo
[2,3-d]pyrimidine (19). Compound 19 was synthesized according to
the procedure described for compound 15. The reaction timed11 h.
Addition of CuI in an amount 1.0 mol % was started after 4 h of
reflux and repeated after every 2 h till the total amount CuI reached
5.0 mol %. The isolation and purification was carried out analo-
gously 15 by column chromatography using hexane/ethyl acetate
(8:1) as an eluent to give compound 19 (93%) as a colourless solid,
4.1.24. 2,4-Bis[4-(9H-carbazol-9-yl)phenyl]-7-phenyl-7H-pyrrolo
[2,3-d]pyrimidine (22). Method A. Compound 22 was synthesized
according to the procedure described for compound 15. The re-
action timed10 h. Addition of CuI in an amount 2.0 mol % was
started after 2 h of reflux and repeated after every 2 h till the total
amount CuI reached 5.0 mol %. The isolation and purification was
carried out analogously 15 by column chromatography using hex-
ane/ethyl acetate (10:1) as an eluent to give compound 22 as
mp 178.8e179.9 ꢀC. UV (THF),
l, nm (
3
, l molꢃ1 cmꢃ1): 242 (1ꢂ104),
260 (2ꢂ104), 297 (2ꢂ104), 344 (1ꢂ104); dH (DMSO-d6): 3.89 (3H, s,
CH3O), 7.17 (1H, d, J¼3.9 Hz, 5-H), 7.22 [2H, dm, J¼9 Hz, 30,50-H
(N7ePh)], 7.39e7.91 [12H, m, 6-H, 30,50,200-600-H (4-biPh), 30-50-H (4-
Ph), 20,60-H (N7ePh)], 8.06 (1H, d, J¼3.6 Hz, 6-H), 8.34e8.37 [2H, m,
20,60-H (4-Ph)], 8.62 [2H, dm, J¼8.4 Hz, 20,60-H (4-biPh)]; dC (DMSO-
d6): 56.2, 102.2, 114.9, 115.3, 125.9, 127.4, 127.6, 128.5, 128.9, 129.5,
129.7, 129.7, 130.9, 131.1, 131.5, 137.9, 138.5, 140.3, 142.2, 152.7, 157.2,
157.3, 158.7; HRMS (ESI): MHþ, found 454.1910. C31H23N3O requires
454.1914.
a yellow solid. Yield 85%, mp 267e268 ꢀC. UV (THF),
l
, nm ( ,
3
l molꢃ1 cmꢃ1): 210 (8ꢂ104), 236 (10ꢂ104), 254 (7ꢂ104), 281
(4ꢂ104), 292 (4ꢂ104), 342 (4ꢂ104); dH (CDCl3): 7.19 (1H, d, J¼3.6 Hz,
5-H), 7.35e7.79 [18H, m, 6-H, 20,60-H (N7ePh), 30,50,200,300,600,700-H
(2-carbazolyl, 4-carbazolyl)], 7.88e7.99 [2H, m, 100,800-H (4-
carbazolyl)], 7.99e8.02 [2H, m, 100,800-H (2-carbazolyl)], 8.19e8.24
[4H, m, 400,500-H (2-carbazolyl, 4-carbazolyl)], 8.63 [2H, dm,
J¼8.7 Hz, 20,60-H (4-carbazolyl)], 8.95 [2H, dm, J¼8.7 Hz, 20,60-H (2-
carbazolyl)]; dC (CDCl3): 102.4, 110.2, 110.3,115.3, 120.3, 120.6, 120.6,
120.7, 123.8, 123.9, 124.2, 126.3, 126.4, 127.0, 127.2, 127.4, 129.5,
129.8, 129.9, 130.9, 137.7, 137.8, 137.9, 139.3, 139.8, 140.9, 140.98,
153.1, 157.1, 158.0; HRMS (ESI): MHþ, found 678.2641. C48H31N5
requires 678.2652.
4.1.22. 4-[2-(Biphenyl-4-yl)-4-phenyl-7H-pyrrolo[2,3-d]pyrimidin-
7-yl]benzonitrile (20). A solution of compound 12 (0.05 g,
0.14 mmol) in anhydrous dioxane (6 mL) was flushed with argon
and 1.0 mol % CuI, anhydrous K3PO4 (0.053 g, 0.25 mmol), 4-
iodobenzonitrile (0.027 g, 0.12 mmol), 10.0 mol % (ꢁ)-trans-1,2-
diaminocyclohexane were added under stirring and argon flow.
The reaction mixture was stirred under reflux for 4 h and 1.0 mol %
of CuI was added. Then every hour 1.0 mol % of CuI was added to the
mixture till the total amount of CuI reached 5.0 mol %. Then after an
Method B. A solution of compound 5e (0.20 g, 0.33 mmol) in
anhydrous toluene (5 mL) was flushed with argon and iodobenzene
(0.08 mL, 0.73 mmol), 10.0 mol % 1,10-phenanthroline, Cs2CO3
(0.22 g, 0.66 mmol) were added under stirring and argon flow. The
reaction mixture was heated to 100 ꢀC and 10.0 mol % CuI was
added. The reaction mixture was stirred under reflux for 16 h. Then
toluene was evaporated under reduced pressure to dryness and
water (5 mL) was added to dissolve inorganic salts. The obtained
solution was extracted with ethyl acetate (3ꢂ25 mL), organic layer
was dried with Na2SO4, ethyl acetate removed by distillation under
reduced pressure and the solid purified by column chromatography
using hexane/benzene as an eluent to give compound 22 (0.11 g,
49%) as a yellow solid, mp 267e268 ꢀC.
hour 1.0 mol
%
CuI and 10.0 mol
%
(ꢁ)-trans-1,2-
diaminocyclohexane were added. Addition of 1.0 mol % of CuI
was continued every hour till amount of CuI reached 10.0 mol %.
Total reaction time was 25 h. After cooling the reaction mixture to
room temperature ethyl acetate (5 mL) was added, resulting solu-
tion was filtered through a layer of silica gel eluting with ethyl
acetate. The filtrate was concentrated under reduced pressure, the
residue was dissolved in a minimal amount of tetrachloromethane
and purified by column chromatography using hexane/ethyl ace-
tate (8:1) as an eluent to give compound 20 (0.051 g, 95%) as
4.1.25. 2,4-Bis[4-(9H-carbazol-9-yl)phenyl]-7-(4-methoxyphenyl)-
7H-pyrrolo[2,3-d]pyrimidine (23). A solution of compound 5e
(0.15 g, 0.25 mmol) in anhydrous dioxane (3 mL) was flushed with
argon and 1.0 mol % CuI, anhydrous K3PO4 (0.11 g, 0.52 mmol), 4-
a
yellowish solid, mp 222e222.7 ꢀC. UV (THF),
l,
nm
( 3 ,
l molꢃ1 cmꢃ1): 280 (3ꢂ104), 332 (1ꢂ104); dH (DMSO-d6): 7.26 (1H,
d, J¼3.9 Hz, 5-H), 7.43e7.87 [10H, m, 6-H, 30,50,200-600-H (4-biPh), 30-
50-H (Ph)], 8.14 [2H, dm, J¼8.7 Hz, 20,60-H (N7ePh)], 8.28 (1H, d,
J¼3.9 Hz, 6-H), 8.31e8.39 [4H, m, 20,60-H (Ph), 30,50-H (N7ePh)],
8.63 [2H, dm, J¼8.7 Hz, 20,60-H (4-biPh)]; dC (DMSO-d6): 104.1,
109.4, 115.6, 119.3, 124.2, 127.5, 127.6, 128.6, 129.0, 129.4, 129.5,
iodoanisole (0.06 g, 0.26 mmol), 10.0 mol
%
(ꢁ)-trans-1,2-
diaminocyclohexane were added under stirring and argon flow.
The reaction mixture was stirred under reflux and every 2 h
1.0 mol % of CuI was added to the reaction mixture till total amount

338
J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
of CuI reached 5.0 mol %. Then after 2 h 2.0 mol % CuI and 10.0 mol %
(ꢁ)-trans-1,2-diaminocyclohexane were added. Total reaction time
was 19 h. After cooling the reaction mixture to room temperature
ethyl acetate (5 mL) was added, resulting solution was filtered
through a layer of silica gel eluting with ethyl acetate. The filtrate
was concentrated under reduced pressure, the residue was dis-
solved in a minimal amount of tetrachloromethane and purified by
column chromatography using hexane/ethyl acetate (8:1) as an
eluent to give compound 23 (0.09 g, 51%) as a yellowish solid, mp
20,60-H (N7ePh)], 7.84e7.91 [4H, m, 100,800-H (2-carbazolyl, 4-
carbazolyl)], 8.20e8.25 [4H, m, 400,500-H (2-carbazolyl, 4-
carbazolyl)], 8.63 [2H, dm, J¼8.7 Hz, 20,60-H (4-carbazolyl)], 8.95
[2H, dm, J¼8.7 Hz, 20,60-H (2-carbazolyl)]; dC (CDCl3): 102.1, 110.2,
110.3,115.2,120.3,120.5,120.6,120.7,123.6,123.8,123.9,124.2,124.8,
124.9,126.3,126.4,127.1,127.4,129.6,129.7,129.9,130.9,132.2,137.7,
138.0,139.3,139.8,140.8,140.9,147.0,147.8,152.9,157.1,157.9; HRMS
(ESI): MHþ, found 845.3370. C60H40N6 requires 845.3387.
186.5e187.1 ꢀC. nmax (KBr) 1517 cmꢃ1 (OCH3); UV (THF),
l, nm (
3 ,
4.1.28. 2-(4-Ethoxyphenyl)-4-(4-methoxyphenyl)-7-phenyl-7H-pyr-
rolo[2,3-d]pyrimidine (26). Method A. Compound 26 was synthe-
sized according to the procedure described for compound 15. The
reaction timed9.5 h. Addition of CuI in an amount 1.0 mol % was
started after 1 h of reflux and repeated after every 2 h till the total
amount CuI reached 5.0 mol %. The isolation and purification was
carried out analogously 15 by column chromatography using
dichloromethane as an eluent to give compound 26 (0.05 g, 99%) as
l molꢃ1 cmꢃ1): 210 (8ꢂ104), 237 (10ꢂ104), 255 (7ꢂ104), 292
(5ꢂ104), 342 (4ꢂ104); dH (CDCl3): 3.97 (3H, s, CH3O), 7.14 (1H, d,
J¼3.6 Hz, 5-H), 7.18e7.21 [2H, m, 30,50-H (4-carbazolyl)], 7.36e7.66
[13H, m, 6-H, 30,50-H (N7ePh), 30,50,200,300,600,700-H (2-carbazolyl),
200,300,600,700-H (4-carbazolyl)], 7.77 [2H, dm, J¼8.7 Hz, 20,60-H
(N7ePh)], 7.84e7.91 [4H, m, 100,800-H (2-carbazolyl, 4-carbazolyl)],
8.20e8.25 [4H, m, 400,500-H (2-carbazolyl, 4-carbazolyl)], 8.62 [2H,
dm, J¼8.4 Hz, 20,60-H (4-carbazolyl)], 8.95 [2H, dm, J¼8.4 Hz, 20,60-H
(2-carbazolyl)]; dC (CDCl3): 55.9, 101.9, 110.2, 110.3, 114.9, 115.0,
120.3, 120.6, 120.6, 120.7, 123.8, 123.9, 125.7, 126.3, 126.4, 127.0,
127.4, 129.9, 129.98, 130.9, 131.0, 137.7, 138.0, 139.3, 139.7, 140.8,
140.9, 153.0, 156.9, 157.9, 158.8; HRMS (ESI): MHþ, found 708.2751.
C49H33N5O requires 708.2758.
a colourless solid, mp 188.3e189.8 ꢀC. UV (THF),
l
, nm ( ,
3
l molꢃ1 cmꢃ1): 291 (2ꢂ104), 330 (1ꢂ104); dH (CDCl3): 1.49 (3H, t,
J¼6.9 Hz, Me), 3.96 (3H, s, OCH3), 4.15 (2H, q, J¼6.9 Hz, CH2O), 6.48
(1H, d, J¼3.9 Hz, 5-H), 7.04 [2H, dm, J¼9 Hz, 30,50-H (4-EtOC6H4)],
7.15 [2H, dm, J¼9 Hz, 30,50-H (4-MeOC6H4)], 7.40e7.43 [1H, m, 40-H
(N7ePh)], 7.55 (1H, d, J¼3.9 Hz, 6-H), 7.59e7.64 [2H, m, 30,50-H
(N7ePh)], 7.93 [2H, dm, J¼8.4 Hz, 20,60-H (N7ePh)], 8.31 [2H, dm,
J¼9 Hz, 20,60-H (4-MeOC6H4)], 8.63 [2H, dm, J¼9 Hz, 20,60-H (4-
EtOC6H4)]; dC (CDCl3): 15.1, 55.7, 63.7, 102.5, 114.2, 114.3, 114.4,
124.0, 126.7, 128.0, 129.6, 129.9, 130.8, 131.6, 131.8, 138.2, 152.9,
157.5, 158.4, 160.7, 161.5; HRMS (ESI): MHþ, found 422.1856.
C27H23N3O2 requires 422.1863.
4.1.26. 4-{2,4-Bis[4-(9H-carbazol-9-yl)phenyl]-7H-pyrrolo[2,3-d]
pyrimidin-7-yl}benzonitrile (24). A solution of compound 5e in an
anhydrous dioxane (3 mL) was flushed with argon and 1.0 mol %
CuI, anhydrous K3PO4 (0.09 g, 0.43 mmol), 4-iodobenzonitrile
(0.06 g, 0.26 mmol), 10 mol % (ꢁ)-trans-1,2-diaminocyclohexane
were added under stirring and argon flow. The reaction mixture
was stirred under reflux and every 2 h 1.0 mol % of CuI was added
to the reaction mixture till an amount of CuI reached 5.0 mol %.
Then after 2 h 2.0 mol % CuI and 10 mol % (ꢁ)-trans-1,2-
diaminocyclohexane were added. Total reaction time was 22 h.
After cooling the reaction mixture to room temperature ethyl ac-
etate (5 mL) was added, resulting solution was filtered through
a layer of silica gel eluting with ethyl acetate. The filtrate was
concentrated under reduced pressure, the residue was dissolved in
a minimal amount of tetrachloromethane and purified by column
chromatography using benzene as an eluent to give compound 24
(0.10 g, 57%) as a yellowish solid, mp 199e199.1 ꢀC. nmax (KBr)
Method B. A solution of compound 27 (0.05 g, 0.15 mmol) in
anhydrous dioxane (5 mL) was flushed with argon and 2.0 mol %
Pd(OAc)2 and 4.0 mol % (2-biphenyl)dicyclohexylphosphine were
added under stirring and argon flow. After 10 min. 4-
ethoxyphenylboronic acid (0.03 g, 0.18 mmol) and K3PO4 (0.08 g,
0.38 mmol) were added. The reaction mixture was stirred under
reflux for 5 h and 0.3 equiv of 4-ethoxyphenylboronic acid and
0.6 equiv of K3PO4 were added additionally. Total reaction time was
20 h. Then dioxane was evaporated under reduced pressure to
dryness and water (5 mL) was added to dissolve inorganic salts. The
obtained solution was extracted with ethyl acetate (3ꢂ25 mL), or-
ganic layer was dried with Na2SO4, ethyl acetate removed by dis-
tillation under reduced pressure, and the solid was purified by
column chromatography using dichloromethane to give compound
26 (0.04 g, 64%) as a colourless solid, mp 188.3e189.8 ꢀC.
2226 cmꢃ1 (CN); UV (THF),
l
, nm (
3
, l molꢃ1 cmꢃ1): 210 (12ꢂ104),
236 (10ꢂ104), 256 (8ꢂ104), 284 (6ꢂ104), 291 (5ꢂ104), 342 (4ꢂ104);
dH (CDCl3): 7.23 (1H, d, J¼3.9 Hz, 5-H), 7.32e7.41 [4H, m, 30,50-H (2-
carbazolyl, 4-carbazolyl)], 7.48e7.61 [8H, m, 200,300,600,700-H (2-
carbazolyl, 4-carbazolyl)], 7.72 (1H, d, J¼3.9 Hz, 6-H), 7.79e7.91
[4H, m, 100,800-H (2-carbazolyl, 4-carbazolyl)], 7.97 [2H, dm,
J¼8.7 Hz, 20,60-H (N7ePh)], 8.20e8.24 [6H, m, 30,50-H (N7ePh),
400,500-H (2-carbazolyl, 4-carbazolyl)], 8.59 [2H, dm, J¼8.4 Hz, 20,60-
H (4-carbazolyl)], 8.94 [2H, dm, J¼8.7 Hz, 20,60-H (2-carbazolyl)]; dC
(CDCl3): 104.1, 110.1, 110.2, 110.3, 115.6, 118.6, 120.4, 120.7, 120.7,
123.8, 123.9, 126.3, 126.4, 127.1, 127.5, 128.1, 128.6, 130.0, 130.9,
133.8, 137.1, 137.4, 139.7, 140.1, 140.8, 140.9, 141.6, 153.4, 157.7,
158.5; HRMS (ESI): MHþ, found 703.2597. C49H30N6 requires
703.2605.
4.1.29. 2-Chloro-4-(4-methoxyphenyl)-7-phenyl-7H-pyrrolo[2,3-d]
pyrimidine (27). A solution of compound 4f (0.20 g, 0.77 mmol) in
anhydrous dioxane (10 mL) was flushed with argon and 1.0 mol %
CuI, anhydrous K3PO4 (0.29 g, 1.37 mmol), iodobenzene (0.072 mL,
0.64 mmol), 10.0 mol % (ꢁ)-trans-1,2-diaminocyclohexane were
added under stirring and argon flow. The reaction mixture was
stirred under reflux for 2 h and 1.0 mol % of CuI was added. Addition
ofportions1.0 mol% CuItothereactionmixturewas continuedevery
hour till amount of CuI reached 5.0 mol %. Then after 2 h 1.0 mol % CuI
and 10.0 mol % (ꢁ)-trans-1,2-diaminocyclohexane were added. Ad-
dition of CuI was continued every hour in portions 1.0 mol % till
amount of CuI reached 10.0 mol %. Then after 2 h 2.0 mol % CuI and
10.0 mol % (ꢁ)-trans-1,2-diaminocyclohexane were added. Total
reaction time was 33 h, total amount of CuId12.0 mol %, (ꢁ)-trans-
1,2-diaminocyclohexaned30.0 mol %. After cooling the reaction
mixture to room temperature ethyl acetate (5 mL) was added,
resulting solution was filtered through a layer of silica gel eluting
with ethyl acetate. The filtrate was concentrated under reduced
pressure and the residue purified by column chromatography using
benzene as an eluent to give compound 27 (0.08 g, 37%) as a col-
ourless solid, mp 164.4e165.1 ꢀC. dH (CDCl3): 3.95 (3H, s, OCH3), 7.01
4.1.27. 4-{2,4-Bis[4-(9H-carbazol-9-yl)phenyl]-7H-pyrrolo[2,3-d]
pyrimidin-7-yl}-N,N-diphenylaniline (25). Compound 25 was syn-
thesized according tothe proceduredescribed forcompound24. The
reaction timed29 h. The isolation and purification was carried out
analogously 24 by column chromatography using benzene as an
eluent to give compound 25 (59%) as a yellowish solid, mp
290e291 ꢀC. UV (THF),
l
, nm (
3
, l molꢃ1 cmꢃ1): 237 (12ꢂ104), 255
(8ꢂ104), 293 (6ꢂ104), 341 (6ꢂ104); dH (CDCl3): 7.13e7.65 [25H, m, 5-
H, 30,50,200,300,600,700-H (2-carbazolyl, 4-carbazolyl), 30,50,2ꢂ(200e600)-H
(N7ePh), N(Ph)2], 7.70 (1H, d, J¼3.6 Hz, 6-H), 7.78 [2H, dm, J¼8.4 Hz,

J. Dodonova et al. / Tetrahedron 68 (2012) 329e339
339
(1H, d, J¼3.9 Hz, 5-H), 7.11 [2H, dm, J¼8.7 Hz, 30,50-H (MeOC6H4)],
7.44e7.62 [4H, m, 6-H, 30-50-H (N7ePh)], 7.75 [2H, dm, J¼8.1 Hz,
20,60-H (N7ePh)], 8.18 [2H, dm, J¼8.7 Hz, 20,60-H (MeOC6H4)]; dC
(CDCl3): 55.7, 102.6, 114.6, 114.9, 124.3, 127.7, 129.3, 129.7, 129.9,
130.9, 137.3, 152.9, 154.6, 159.9, 162.1; HRMS (ESI): MHþ, found
336.0900. C19H14ClN3O requires 336.0898.
Green, J.; Susa, M.; Wagenknecht, H.; Widler, L. Bioorg. Med. Chem. Lett. 2001, 11,
853e861; (d)Widler, L.; Green, J.; Missbach, M.; Susa, M.; Altmann, E. Bioorg. Med.
Chem. Lett. 2001, 11, 849e852; (e) Choi, H.-S.; Wang, Z.; Richmond, W.; He, X.;
Yang, K.; Jiang, T.; Karanewsky, D.; Gu, X.; Zhou, V.; Liu, Y.; Che, J.; Lee, C. C.;
Caldwell, J.; Kanazawa, T.; Umemura, I.; Matsuura, N.; Ohmori, O.; Honda, T.; Gray,
N.; He, Y. Bioorg. Med. Chem. Lett. 2006, 16, 2689e2692; (f) Harris, C. M.; Ericsson,
A. M.; Argiriadi, M. A.; Barberis, C.; Borhani, D. W.; Burchat, A.; Calderwood, D. J.;
Cunha, G. A.; Dixon, R. W.; Frank, K. E.; Johnson, E. F.; Kamens, J.; Kwak, S.; Li, B.;
Mullen, K. D.; Perron, D. C.; Wang, L.; Wishart, N.; Wu, X.; Zhang, X.; Zmetra, T. R.;
Talanian, R. V. Bioorg. Med. Chem. Lett. 2010, 20, 334e337.
Acknowledgements
7. Gibson, C. L.; Huggan, J. K.; Kennedy, A.; Kiefer, L.; Lee, J. K.; Suckling, C. J.;
Clements, C.; Harvey, A. L.; Hunter, W. N.; Tulloch, L. B. Org. Biomol. Chem. 2009,
7, 1829e1842.
8. Hess, S.; Muller, C. E.; Frobenius, W.; Reith, U.; Klotz, K.-N.; Eger, K. J. Med. Chem.
2000, 43, 4636e4646.
Research Council of Lithuania is greatly acknowledged for fi-
nancial support (project No. MIP-65/2010).
9. (a) Naus, P.; Pohl, R.; Votruba, I.; Dzubak, P.; Haiduch, M.; Ameral, R.; Birkus, G.;
Wang, T.; Ray, A. S.; Mackman, R.; Cihlar, T.; Hocek, M. J. Med. Chem. 2010, 53,
460e470; (b) Jung, M.-H.; Kim, H.; Choi, W.-K.; El-Gamal, M. I.; Park, J.-H.; Yoo,
K. H.; Sim, T. B.; Lee, S. H.; Baek, D.; Hah, J.-M.; Cho, J.-H.; Oh, C.-H. Bioorg. Med.
Chem. Lett. 2009, 19, 6538e6543.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.10.040. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
10. Seela, F.; Steker, H. Liebigs Ann. Chem. 1984, 1719e1730.
11. Berry, D. A.; Jung, K.-Y.; Wise, D. S.; Sercel, A. D.; Pearson, W. H.; Mackie, H.;
Randolph, J. B.; Somers, R. L. Tetrahedron Lett. 2004, 45, 2457e2461.
12. Tumkevicius, S.; Dodonova, J.; Kazlauskas, K.; Masevicius, V.; Skardziute, L.;
Jursenas, S. Tetrahedron Lett. 2010, 51, 3902e3906.
References and notes
13. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457e2483; (b) Suzuki, A. J.
Organomet. Chem. 1999, 576, 147e168; (c) Gholap, A. R.; Toti, K. S.; Shirazi, F.;
Deshpande, M. V.; Srinivasan, K. V. Tetrahedron 2008, 64, 10214e10223; (d) Li,
J.; Zhang, X.; Xie, Y. Synlett 2005, 1897e1900; (e) Yin, J.; Rainka, M. P.; Zhang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 1162e1163; (f) Kotha, S.; Lahiri, K.;
Kashinath, D. Tetrahedron 2002, 58, 9633e9695; (g) Bellina, F.; Carpita, A.;
Rossi, R. Synthesis 2004, 2419e2440; (h) Schroter, S.; Stock, C.; Bach, T. Tetra-
hedron 2005, 61, 2245e2267; (i) Fairlamb, I. J. S. Chem. Soc. Rev. 2007, 36,
1036e1045.
14. (a) Sakamoto, T.; Kondo, Y.; Sato, S.; Yamanaka, H. Tetrahedron Lett. 1994, 35,
2919e2920; (b) Wu, T. Y. H.; Schultz, P. G.; Ding, S. Org. Lett. 2003, 5,
3587e3590; (c) Edstrom, E. D.; Wei, Y. J. Org. Chem. 1993, 58, 403e407; (d)
Klecka, M.; Pohl, R.; Klepetarova, B.; Hocek, M. Org. Biomol. Chem. 2009, 7,
866e868.
1. (a) Hughes, G.; Bryce, M. R. J. Mater. Chem. 2005, 15, 94e107; (b) Wong, W. Y.;
Zhou, G.-J.; Yu, X.-M.; Kwok, H.-S.; Lin, Z. Adv. Funct. Mater. 2007, 17, 315e323;
(c) Tao, Y.; Wang, Q.; Yang, C.; Wang, Q.; Zhang, Z.; Zou, T.; Qin, J.; Ma, D. Angew.
Chem., Int. Ed. 2008, 47, 8104e8107.
2. (a) Wong, K.-T.; Hung, T. S.; Lin, Y.; Wu, C.-C.; Lee, G.-H.; Peng, S.; Chou, C. H.; Su,
Y. O. Org. Lett. 2002, 4, 513e516; (b) Wu, C. C.; Lin, Y. T.; Chiang, H. H.; Cho, T. Y.;
Chen, C. W.; Wong, K. T.; Liao, Y. L.; Lee, G. H.; Peng, S. M. Appl. Phys. Lett. 2002,
81, 577e579; (c) Yamaguchi, Y.; Kobayashi, S.; Wakamiya, T.; Matsubara, Y.;
Yoshida, Z. Angew. Chem., Int. Ed. 2005, 44, 7040e7044; (d) Achelle, S.; Ra-
mondenc, Y.; Marsais, F.; Ple, N. Eur. J. Org. Chem. 2008, 3129e3140; (e) Jaung, J.-
Y. Dyes Pigm. 2006, 71, 245e250.
3. (a) Petitjean, A.; Khoury, R. G.; Kyritsakas, N.; Lehn, J.-M. J. Am. Chem. Soc. 2004,
126, 6637e6647; (b) Schull, G.; Douillard, L.; Fiorini-Debuisschert, C.; Charra, F.;
Mathevet, F.; Kreher, D.; Attias, A.-J. Adv. Mater. 2006, 18, 2954e2957.
4. (a) Bunzli, J.-C. G.; Piguet, C. Chem. Soc. Rev. 2005, 34, 1048e1077; (b) Diring, S.;
Retailleaub, P.; Ziessel, R. Tetrahedron Lett. 2007, 48, 8069e8073.
15. Dodonova, J.; Uogintaite, I.; Masevicius, V.; Tumkevicius, S. Chem. Heterocycl.
Compd. 2010, 46, 1122e1126.
16. (a) Saxena, N. K.; Hagenow, B. M.; Genzlinger, G.; Turk, S. R.; Drach, J. C.;
Townsend, L. B. J. Med. Chem. 1988, 31, 1501e1506; (b) Kazimierczuk, Z.; Cottam,
H. B.; Revankar, G. R.; Robins, R. K. J. Am. Chem. Soc. 1984, 106, 6379e6382.
17. Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
7727e7729.
18. Adams, M. J.; Highfield, J. G.; Kirkbright, G. F. Anal. Chem. 1977, 49, 1850e1852.
19. Mello, J. C.; Wittmann, H. F.; Friend, R. H. Adv. Mater. 1997, 9, 230e232.
5. Mohamed, M. S.; El-Domany, R. A.; El-Hameed, R. H. A. Acta Pharm. 2009, 59,
145e158.
6. (a) Wiesner, J. B.; Ugarkar, B. G.; Castellino, A. J.; Barankiewicz, J.; Dumas, D. P.;
Gruber, H. E.; Foster, A. C.; Erion, M. D. J. Pharmacol. Exp. Ther. 1999, 289,
1669e1677; (b) Calderwood, C. J.; Johnston, D. N.; Munschauer, R.; Rafferty, P.
Bioorg. Med. Chem. Lett. 2002, 12, 1683e1686; (c) Altmann, E.; Missbach, M.;