3-Formylchromones, acylpyruvates, and chalcone as valuable substrates for the syntheses of fused pyridines

Article abstract of DOI:10.1055/s-0029-1218842

The reaction of electron-rich aminoheterocycles with 1,3-CCC- dielectrophiles, such as 3-formylchromones, acylpyruvates, and chalcone, provided diversely fused pyridines. Starting from 5-amino-1-(2,3-O- isopropylidene - d-ribofuranosyl)-1H-pyrazole, nucleosides containing a pyrazolo[3,4-b]pyridine fragment were obtained, which can be considered as adenosine deaminase (ADA) inhibitors. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218842

PAPER
2749
3-Formylchromones, Acylpyruvates, and Chalcone as Valuable Substrates for
the Syntheses of Fused Pyridines
S
ynthesis of 1-Des
i
azapur
k
ine Isosterestor O. Iaroshenko,*a,b Satenik Mkrtchyan,b Dmitriy M. Volochnyuk,a,c Peter Langer,*b
Vyacheslav Ya. Sosnovskikh,*d Dmytro Ostrovskyi,a Sergii Dudkin,b Anton V. Kotljarov,e Mariia Miliutina,f
Iryna Savych,f Andrei A. Tolmacheva,c
a
National Taras Shevchenko University, 62 Volodymyrska St., Kyiv-33, 01033, Ukraine
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b
Fax +49(381)4986412; E-mail: viktor.iaroshenko@uni-rostock.de; E-mail: iva108@gmail.com
Enamine Ltd., 23 A. Matrosova st., 01103 Kyiv, Ukraine
Department of Chemistry, Ural State University, 51 Lenina Ave., 620083 Ekaterinburg, Russian Federation
c
d
E-mail: vyacheslav.sosnovskikh@usu.ru
Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia
Organic Chemistry Department, National Kharkiv V. N. Karazin University, sq. Svobody 4, Kharkiv-77, 61077, Ukraine
e
f
Received 9 April 2010
tives, such as pyrido[2,3-d]pyrimidines.11 Solvent- and
Abstract: The reaction of electron-rich aminoheterocycles with
catalyst-free one-pot syntheses of functionalized 1,8-
1,3-CCC-dielectrophiles, such as 3-formylchromones, acylpyru-
naphthyridines and quinolines have been developed by
vates, and chalcone, provided diversely fused pyridines. Starting
microwave-mediated reactions of chalcones and a-ami-
from
5-amino-1-(2,3-O-isopropylidene-b-D-ribofuranosyl)-1H-
pyrazole, nucleosides containing a pyrazolo[3,4-b]pyridine frag- nopyridines.12 Quinolines are available also by palladium-
ment were obtained, which can be considered as adenosine deami-
catalyzed Heck reaction of 2-iodoanilines with chal-
cones.13
nase (ADA) inhibitors.
Key words: aminoheterocycles, 3-formylchromones, acylpyru-
Very recently, we reported14 the synthesis of two scaffolds
vates, chalcone, fused pyridines, annulation reaction, nucleosides
of hetero analogues of cinchoninic esters containing 7-
substituted pyrrolo[2,3-b]pyridine-4-carboxylic acid and
5-substituted thiazolo[4,5-b]pyridine-7-carboxylic acid
Fused pyridines including 1-desazapurines and their ana-
moieties. As a continuation of our studies on the synthetic
logues are important and interesting objectives for mod-
potential of electron-rich heterocyclic amines 4–9,15,16 and
ern medical chemistry.1 Our interest in pyridine and
due to the increasing importance of fused pyridines in
pyrimidine heterocycles containing imidazole, pyrazole,
biology and pharmacology,1–6 we decided to investigate
and thiazole rings is mainly as a result of the known bio-
their reactions with 1,3-dielectrophiles, such as 3-formyl-
chromones 1, acylpyruvates 2 and chalcone (3) (Figures 1
and 2).
logical activity of these systems reported in the literature.
Thus, pyrazolo[3,4-b]pyridine derivatives have been re-
ported to be a new class of cdk2 inhibitor2 and potent and
selective cyclin-dependent kinase and glycogen synthase
O
kinase-3 (GSK-3) inhibitors.3 Pyrazolo[3,4-b]pyridines
O
CHO
are also reported to possess antimicrobial,4 antichagasic,5
antileishmanial, and anti-inflammatory activity.6
R
Ph
Ph
MeO
R
O
O
O
O
On the other hand, reactions of 4-oxo-4H-chromene-3-
carbaldehydes (3-formylchromones, 1) and acylpyruvates
2, having three electrophilic centers, with nucleophiles,
which also possess several reactive centers, can lead in
several directions and are, therefore, of interest from the
point of view of their chemo- and regioselectivity.7 Re-
cent advances in the chemistry of these molecules include
cyclocondensation reactions with pyridine8 and
pyrimidine9 derivatives and syntheses of fluorinated prod-
ucts starting from 3-(polyfluoroacyl)chromones.10
1 (R = H, 6,8 -dichloro)
2 (R = Ar, Me)
3
Figure 1 Structures of the 1,3-CCC-dielectrophiles used
N
N
NH2
NH2
NH2
R
Me
N
N
X
Ph
Me
4 (X = O, S)
5 (R = H, SMe)
6
Me
N
O
S
Several symmetric and nonsymmetric chalcones have
been used for the synthesis of condensed pyridine deriva-
N
NH2
NH2
NH2
S
Alk2N
Ph
N
N
N
H
Me
8
7
9
Figure 2 Structures of the 1,3-CCN-dinucleophiles used
SYNTHESIS 2010, No. 16, pp 2749–2758
x
x.
x
x
.
2
0
1
0
Advanced online publication: 29.06.2010
DOI: 10.1055/s-0029-1218842; Art ID: P05610SS
© Georg Thieme Verlag Stuttgart · New York

2750
V. O. Iaroshenko et al.
PAPER
The aminoazoles 4–9 were initially investigated for their In our earlier publications we established the structure of
enamine reactivity in [3+3] cyclocondensation with 3- related fused pyridines by X-ray experiments.14a,b The
1
formylchromones 1. Thus, when 3-formylchromones 1 structures of pyridines 10–12 were confirmed by H and
were reacted with 4–9 in refluxing acetic acid or methanol 13C NMR spectroscopy and mass spectra and are in good
with a catalytic amount of 4-toluenesulfonic acid, workup agreement with earlier synthesized heterocyclic pat-
of the reaction mixture furnished b-salicyloyl-substituted terns.9,14a,b,16 Moreover, the protons of the CO2Me group
heteroannulated pyridines 10a–n in high yields. In this of compounds 11 show ROESY correlations with the pro-
case, pyranone ring opening takes place with the subse- tons of the neighboring groups also confirming the consti-
quent annulation of the pyridine core to give the amino- tution of 11.
heterocycle moiety. This reaction proceeds in a
straightforward fashion without formation of any possible
byproducts (Scheme 1, Table 1).
Esters 11 are crystalline compounds, which were purified
by recrystallization from an appropriate solvent. These es-
ters can be easily transformed to hydrazides 13a–d by
treatment of 11 with hydrazine hydrate (5 equiv) in meth-
O
OH
anol. The synthesis of acids 14a–h, the isosteric analogues
of cinchoninic acid, has been achieved by treatment of
11a–h with sodium hydroxide in methanol. After treat-
ment of the corresponding sodium salts by either 0.1 M
HCl or acetic acid, acids 14 were obtained in high yields.
Starting from 14 we have successfully obtained the corre-
sponding acid chlorides by treatment of 14 with two
equivalents of thionyl chloride in anhydrous toluene un-
der reflux for three hours. Subsequent reaction of the acid
chlorides in 1,4-dioxane with aromatic and aliphatic
amines gave amides 15a–h (Scheme 2).
1
Het
4–9
Het
Ph
N
NH2
R1
10a–n (61–93%)
3 + 6–8
2
CO2Me
Ph
Het
Het
Het
N
R2
N
H
Ph
N
Ph
11a–h (37–87%)
12a–e (43–72%)
12'
CO2Me
CONHNH2
Scheme 1 Reagents and conditions: (i) AcOH, reflux, 2 h (for 8, 9);
(ii) MeOH, PTSA, inert atmosphere, reflux 2–3 h (for 6, 7); (iii)
DMF–AcOH–H2O, 140 °C (for 4, 5).
i
Het
Het
N
R1
N
R1
13a–d (51–93%)
11
Similarly, treatment of acylpyruvates 2 with heterocyclic
amine 4–9 in acetic acid under reflux resulted in the for-
mation of fused pyridines 11a–h in good yields. 5-Ami-
noimidazoles 6 and 7 are unstable in acidic media and can
not tolerate oxygen, thus we conducted these reactions in
absolute methanol under an atmosphere of dry nitrogen in
the presence of a catalytic amount of 4-toluenesulfonic
acid. Benzofuran- and benzothiophen-2-amines 4, as well
as 1-phenyl-1H-imidazol-5-amines 5, which were gener-
ated in situ following the previous described Curtius
protocol15a,16 starting from the corresponding acyl azides,
reacted with 3-formylchromones 1 and acylpyruvates 2
under the conditions of the aminoheterocycle generation
(DMF–AcOH–H2O, 135–140 °C). Interestingly, the cy-
clization of 2 with aminoazoles 4–9 was to be highly regio-
selective and never yielded isomers with the reversed
positions of the R and CO2Me groups in the pyridine ring.
ii
CO2H
N
CONR2
2
iii
Het
Het
R1
N
R1
15a–h (58–71%)
14a–h (65–92%)
Scheme 2 Reagents and conditions: (i) N2H4·H2O, MeOH reflux;
(ii) (a) NaOH, MeOH, reflux, (b) 0.1 M HCl; (iii) (a) SOCl2 (2 equiv),
toluene reflux, (b) R2 NH, 1,4-dioxane, reflux.
2
A variety of functionalized purines17 and purine isosters18
have been recognized as adenosine deaminase (ADA) in-
hibitors. Some of them14–16 were synthesized in our group
and their pharmaceutical evaluation is currently under in-
vestigation. Our dual interest in this work was to synthe-
size a new series of hybrid structures containing the
pyrazolo[3,4-b]pyridine ring and a carbohydrate (b-D-ri-
bofuranose) moiety as the recognition element, which are
promising scaffolds for potential ADA enzymes inhibi-
tors.
To further explore the synthetic scope and reactivity of the
heterocyclic amines to obtain fused pyridines, condensa-
tion of 6–8 with chalcone 3 was investigated. Thus, when
6–8 were subjected to reaction with 3 in refluxing acetic
acid or methanol under an inert atmosphere, the corre-
sponding pyridines 12a–e were obtained in good yields
via Michael addition and intramolecular cyclization. It
should be noted that heterocyclic products in these reac-
tions were not isolable as the dihydro derivatives, which
indicates the high propensity of the expected fused dihy-
dropyridines 12¢ to oxidation (Scheme 1, Table 1).
We decided to perform the synthesis of 6-methyl-1-(b-D-
ribofuranosyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic
acid (18a) from acetylpyruvate 2 (R = Me) and iso-AIRs
16
[5-amino-1-(2,3-O-isopropylidene-b-D-ribofurano-
syl)-1H-pyrazole]. Proton catalysis of the reaction is not
advisable15c and the desired pyridine ring annulation pro-
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Desazapurine Isosteres
2751
ceeded smoothly in absolute N,N-dimethylformamide at
135 °C under an inert atmosphere for 18 hours, delivering
the pyrazolo[3,4-b]pyridine 17 in 41% yield (Scheme 3).
Hydrolysis of the ester function in 17 was conducted us-
ing sodium hydroxide in methanol and treatment of the re-
sulting sodium salt with trifluoroacetic acid–water (9:1)
leads to deprotection of the sugar to give acid 18a. Syn-
thesis of 18a starting from 16 was conducted as a one-pot,
two-stage reaction. Ester 17 was transformed into hy-
drazide 18b by treatment with five equivalents of hydra-
zine hydrate in methanol, its subsequent reaction with
trifluoroacetic acid–water (9:1) gave riboside 18c in 61%
yield (Scheme 3).
N
O
N
O
NH2
O
HO
MeO
+
O
O
O
16
2
i
CO2Me
N
COR1
N
O
N
N
N
N
O
O
HO
HO
ii–iv
In summary, we reported a cyclocondensation reaction in-
volving electron-rich aminoheterocycles and a number of
1,3-CCC-dielectrophiles. The present work demonstrates
the versatility of 3-formylchromones, acylpyruvates, and
chalcone in one-pot synthetic procedures leading to di-
versely fused pyridines. Applying typical transformations
of the ester group, the corresponding acids, amides, and
hydrazides were obtained in high yields. Moreover, the
synthesis of potential inhibitors of ADAs enzymes using
iso-AIRs was performed.
R2O
OR2
O
17 (41%)
18a–c
a: R1 = OH, R2 = H, 59%;
b: R1 = NHNH2, R2–R2 = CMe2, 57%
c: R1 = NHNH2, R2 = H, 61%
Scheme 3 Reagents and conditions: (i): DMF, inert atmosphere,
120 °C, 24 h; (ii) NaOH, MeOH, r.t. (for 18a); (iii) N2H4·H2O, MeOH,
reflux (for 18b); (iv) TFA–H2O (9:1), r.t., 1 h (for 18b → 18c).
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
1H: 6.96–7.03 (m, 2 H), 7.43–7.53 (m, 2 H), 7.61 (t, J = 7.2, 1 H),
7.77 (d, J = 7.2, 1 H), 8.31 (d, J = 7.2, 2 H), 8.71 (s, 1 H), 8.95 (s, 1
H), 10.45 (s, 1 H, OH)
O
OH
161–162
(i-PrOH)
13C: 112.0, 116.2, 116.9, 119.4, 121.7, 122.8, 124.2, 124.5, 129.4,
130.2, 130.8, 131.8, 133.9, 148.6, 154.4, 157.0, 164.2, 195.2
MS: 290 (22) [M+ + 1], 289 (100) [M+], 288 (86), 196 (27), 170
(10), 169 (86), 168 (28), 144 (10), 140 (35), 121 (41), 120 (41), 113
(11), 93 (14), 65 (21)
10a
93
O
N
1H: 7.03–7.10 (m, 2 H), 7.52–7.65 (m, 4 H), 8.11 (d, J = 7.2, 1 H),
8.51 (d, J = 7.2, 1 H), 8.83 (d, J = 7.2, 1 H), 9.02 (s, 1 H), 10.47 (s,
1 H, OH)
O
OH
154–156
(i-PrOH)
10b
10c
87
13C: 117.5, 119.9, 123.9, 124.7, 126.2, 127.0, 128.9, 129.1, 130.4,
131.0, 131.5, 132.7, 134.6, 137.6, 149.8, 157.7, 164.6, 196.0
MS: 306 (19) [M+ + 1], 305 (100) [M+], 288 (35), 196 (17), 212, 83,
184 (14), 170 (81), 168 (22), 145 (21), 140 (57), 121 (53), 113 (28)
S
N
1H: 2.73 (s, 3 H, SCH3), 6.93–7.03 (m, 2 H), 7.41–7.47 (m, 2 H),
7.55–7.65 (m, 5 H), 8.22 (s, 1 H), 8.53 (s, 1 H), 10.46 (br s, 1 H, OH)
13C: 14.3, 117.3, 119.7, 125.2, 125.9, 128.0, 129.2, 130.1, 130.2,
131.1, 133.6, 134.0, 135.0, 145.3, 152.4, 157.4, 158.2, 196.3
MS: 362 (22) [M+ + 1], 361 (100) [M+], 313 (11), 314 (67), 312
(20), 284 (43), 240 (71), 239 (12), 172 (25), 121 (14), 120 (22), 77
(53)
O
OH
234–235
(i-PrOH)
N
93
MeS
N
N
Ph
1H: 7.35 (s, 1 H), 7. 53 (s, 1 H), 7.63–7.79 (m, 5 H), 8.12 (s, 1 H),
8.49 (s, 1 H), 9.05 (s, 1 H), 10.67 (br s, 1 H, OH)
O
OH
Cl
13C: 123.7, 124.0, 124.0, 124.4, 128.5, 128.6, 128.9, 129.0, 129.7,
130.1, 132.7, 135.1, 135.4, 146.9, 147.2, 149.4, 151.4, 193.8
MS: 385 (23) [M+ + 2], 383 (10) [M+], 383 (34), 222 (17), 196 (17),
195 (100), 194 (22), 188 (14), 167 (16), 140 (15), 77 (20)
N
154–156
(i-PrOH)
10d
10e
89
N
N
Ph
Cl
O
1H: 2.88 (s, 3 H, CH3), 3.95 (s, 3 H, NCH3), 7.40 (s, 1 H), 7.77 (s, 1
H), 8.17 (s, 1 H), 8.61 (s, 1 H), 10.52 (s, 1 H, OH)
13C: 13.7, 28.1, 122.7, 123.0, 126.1, 126.1, 126.6, 127.8, 127.8,
128.5, 131.5, 131.6, 133.2, 144.6, 150.3, 150.6, 156.5, 193.0
MS: 337 (20) [M+ + 1], 336 (15) [M+], 335 (31), 174 (19), 147
(100), 146 (22)
OH
Cl
Cl
N
159
77
Me
(EtOH)
N
N
Me
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

2752
V. O. Iaroshenko et al.
PAPER
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15 (continued)
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
1H: 3.75 (s, 3 H, CH3), 3.91 (s, 3 H, CH3), 7.01–7.09 (m, 2 H), 7.51
(m, 2 H), 8.13 (s, 1 H), 8.69 (s, 1 H), 10.50 (s, 1 H, OH)
13C: 30.7, 34.9, 114.2, 118.0, 120.1, 122.4, 125.7, 126.9, 127.8,
131.5, 133.7, 146.9, 156.4, 172.1, 192.1
O
OH
Me
207–209
(EtOH)
N
10f
61
S
N
Me
MS: 300 (15) [M+ + 1], 299 (100) [M+], 267 (38), 231 (77), 211
(12), 201 (10), 188 (89), 187 (71), 185 (13), 133 (37), 123 (45)
N
1H: 2.06 [s, 4 H, (CH2)2], 3.63 [s, 4 H, N(CH2)2], 6.91–6.97 (m, 2
H), 7.41 (m, 2 H), 8.53 (s, 1 H), 8.58 (s, 1 H), 10.39 (s, 1 H, OH)
13C: 25.2, 49.8, 116.9, 119.0, 124.3, 125.5, 125.2, 129.9, 130.8,
132.8, 149.9, 156.1, 167.0, 172.0, 194.0
O
OH
172–173
(i-PrOH)
10g
10h
71
S
MS: 327 (10) [M+ + 2], 326 (17) [M+ + 1], 325 (100) [M+], 324 (35),
297 (36), 296 (14), 270 (19), 232 (12), 206 (12), 205 (78), 204 (14),
177 (60), 176 (15), 150 (31), 121 (26), 65 (13)
N
N
N
1H: 2.06 [s, 4 H, (CH2)2], 3.63 [s, 4 H, N(CH2)2], 7.40 (s, 1 H), 7.75
(s, 1 H), 8.57 (s, 1 H), 8.63 (s, 1 H), 10.48 (s, 1 H, OH)
13C: 25.3, 49.8, 123.2, 123.8, 124.6, 125.2, 128.0, 129.6, 130.9,
131.7, 149.8, 150.3, 167.6, 169.1, 192.0
O
OH
Cl
Cl
S
N
168–170
(EtOH)
73
MS: 395 (70) [M+ + 2], 394 (22) [M+ + 1], 393 (100) [M+], 380 (22),
378 (31), 366 (10), 354 (14), 353 (19), 352 (20), 351 (19), 246 (10),
219 (63), 191 (15), 190 (30), 189 (18), 164 (19), 163 (20), 151 (31),
150 (10), 137 (11), 136 (13), 55 (12), 41 (21)
N
N
1H: 1.66 [s, 6 H, (CH2)3], 3.67 [s, 4 H, N(CH2)2], 6.97–7.00 (m, 2
H), 7.43 (m, 2 H), 8.50 (s, 1 H), 8.53 (s, 1 H), 10.23 (s, 1 H, OH)
13C: 23.5, 25.0, 49.2, 116.6, 119.3, 124.6, 125.2, 125.6, 130.1,
130.2, 133.0, 149.4, 156.3, 167.1, 171.7, 194.4
173–175
Rf = 0.50
(hexane–
EtOAc, 3:1)
O
OH
10i
10j
10k
83
S
MS: 340 (22) [M+ + 1], 339 (100) [M+], 338 (17), 310 (29), 284
(19), 283 (20), 190 (20), 164 (16), 163 (14), 151 (16), 137 (10), 121
(30), 84 (11), 65 (14), 55 (13), 41 (24)
N
N
N
O
OH
1H: 1.22 (t, J = 7.2, 6 H, 2 CH3), 3.58 (q, J = 7.2, 4 H, 2 NCH2),
7.01–7.04 (m, 2 H), 7.49 (m, 2 H), 8.43 (s, 1 H), 8.49 (s, 1 H), 10.57
(s, 1 H, OH)
88
67
138–140
S
Et2N
N
N
1H: 3.67 [s, 4 H, N(CH2)2], 3.75 [s, 4 H, O(CH2)2], 7.11–7.15 (m, 2
H), 7.57 (m, 2 H), 8.48 (s, 1 H), 8.54 (s, 1 H), 10.67 (s, 1 H, OH)
13C: 49.2, 65.7, 117.2, 118.9, 124.5, 125.0, 125.4, 129.8, 130.5,
132.1, 149.7, 156.5, 166.7, 172.2, 194.7
O
OH
211–213
(EtOH)
S
N
MS: 342 (22) [M+ + 1], 341 (100) [M+], 285 (11), 284 (63), 221
(38), 190 (14), 165 (10), 164 (53), 163 (16), 162 (11), 121 (41), 120
(21), 93 (13), 65 (21)
O
N
N
1H: 3.69 [s, 4 H, N(CH2)2], 3.78 [s, 4 H, O(CH2)2], 7.47 (s, 1 H),
7.69 (s, 1 H), 8.51 (s, 1 H), 8.59 (s, 1 H), 10.41 (s, 1 H, OH)
13C: 49.8, 64.9, 122.9, 124.1, 124.4, 125.7, 128.4, 129.2, 131.2,
131.8, 149.7, 150.1, 167.1, 169.7, 192.3
O
OH
Cl
Cl
S
N
256–257
(EtOH)
10l
77
65
MS: 413 (15) [M+ + 3], 412 (16) [M+ + 2], 411 (72) [M+ + 1], 410
(28) [M+], 409 (100), 354 (42), 353 (18), 352 (61), 248 (14), 222
(10), 221 (76), 191 (23), 190 (37), 189 (18), 188 (22), 177 (10), 165
(12), 164 (61), 163 (26), 162 (21), 136 (18), 135 (13)
O
N
N
1H: 6.95–7.00 (m, 2 H), 7.21 (t, J = 7.2, 1 H), 7.38–7.47 (m, 4 H),
8.03 (d, J = 7.2, 2 H), 8.25 (s, 1 H), 8.52 (s, 1 H), 10.77 (s, 2 H, OH,
NH)
O
OH
O
189–192
(EtOH)
10m
13C: 113.6, 116.7, 119.1, 119.6, 124.9, 125.1, 128.9, 130.2, 133.1,
137.63, 137.69, 138.69, 138.72, 158.2, 155.7, 158.5. 192.1
MS: 332 (27) [M+ + 1], 331 (100) [M+], 330 (16), 212 (11), 211
(74), 182 (21), 121 (51), 93 (10), 77 (22), 65 (14)
Ph
N
N
N
H
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Desazapurine Isosteres
2753
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15 (continued)
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
1H: 7.20 (t, J = 7.2, 1 H), 7.41–7.46 (m, 3 H), 7.75 (br s, 1 H), 8.02
(s, 1 H), 8.04 (s, 1 H), 8.31 (br s, 1 H), 8.56 (br s, 1 H, NH), 10.41
(br s, 1 H, OH)
O
OH
Cl
O
Cl
288–289
(EtOH)
13C: 114.3, 119.1, 121.8, 122.0, 123.3, 123.8, 125.0, 128.1, 128.1,
128.9, 129.0, 131.8, 137.4, 138.8, 148.5, 150.1, 158.4, 189.9
MS: 400 (17) [M+ + 1], 399 (25) [M+], 345 (17), 211 (44), 105 (43),
104 (28), 92 (16), 91 (26), 79 (49), 78 (37), 77 (100), 65 (28), 64
(27), 51 (13), 44 (13), 43 (11)
10n
69
Ph
N
N
N
H
1H: 2.68 (s, 3 H, CH3), 4.11 (s, 3 H, OCH3), 7.50 (t, J = 8.0, 1 H),
7.66 (t, J = 8.0, 1 H), 7.73 (s, 1 H), 7.83 (d, J = 8.0, 1 H), 7.99 (d,
J = 8.0, 1 H)
CO2Me
165–166
(EtOH)
11a
11b
11c
78
13C: 24.4, 55.0, 109.8, 112.7, 115.5, 119.7, 123.4, 124.7, 126.7,
129.9, 154.5, 158.1, 163.1, 167.0
O
MS: 242 (11) [M+ + 1], 241 (100) [M+], 200 (13), 170 (14), 169
(19), 157 (17)
N
Me
1H: 2.61 (s, 3 H, CH3), 4.01 (s, 3 H, OCH3), 7.33 (t, J = 7.8, 1 H),
7.49 (t, J = 7.8, 1 H), 7.55 (d, J = 7.8, 1 H), 7.81 (s, 1 H), 8.21 (d,
J = 7.8, 1 H)
155–158
Rf = 0.45
(hexane–
EtOAc, 3:1)
CO2Me
70
13C: 26.7, 53.9, 112.8, 123.2, 126.0, 127.0, 127.7, 129.2, 129.6,
133.0, 140.1, 145.9, 164.1, 167.7
MS: 258 (15) [M+ + 1], 257 (100) [M+], 226 (70), 225 (13), 198
(39), 150 (11), 149 (81), 119 (43), 92 (49), 77 (71)
S
N
Me
1H: 2.51 (s, 3 H, CH3), 2.68 (s, 3 H, SCH3), 4.03 (s, 3 H, OCH3),
7.15 (s, 1 H), 7.37–7.49 (m, 5 H)
CO2Me
13C: 14.1, 24.2, 52.6, 118.2, 125.5, 127.4, 129.3, 129.6, 131.9,
133.7, 151.4, 152.1, 157.5, 165.9
N
185
87
(EtOH)
MeS
MS: 314 (18) [M+ + 1], 313 (100) [M+], 282 (41), 254 (93), 253
(11), 240 (21), 239 (91), 203 (35), 202 (20), 157 (12), 156 (81), 154
(15), 111 (27)
N
N
Me
Ph
1H: 3.97 (s, 3 H, OCH3), 7.46–7.55 (m, 4 H), 7.65–7.72 (m, 2 H),
8.00 (d, J = 7.8, 2 H), 8.12 (s, 1 H), 8.16 (d, J = 7.8, 2 H), 9.05 (s, 1
H)
CO2Me
200–201
(EtOH)
N
11d
11e
11f
11g
85
13C: 52.6, 111.7, 122.8, 123.8, 127.8, 127.9, 128.9, 129.5, 129.6,
130.4, 134.6, 137.6, 146.8, 147.7, 152.1, 165.0
MS: 330 (18) [M+ + 1], 329 (100) [M+], 298 (70), 252 (43)
N
N
Ph
Ph
1H: 2.51 (s, 3 H, 5-CH3), 2.65 (s, 3 H, 2-CH3), 3.89 (s, 3 H, NCH3),
CO2Me
3.99 (s, 3 H, OCH3), 7.78 (s, 1 H)
157–160
(EtOH)
13C: 14.5, 27.0, 29.0, 53.3, 114.3, 124.7, 135.3, 140.1, 144.5, 158.1,
N
37
Me
Me
S
168.1
MS: 220 (14) [M+ + 1], 219, (100) [M+], 160 (22), 189 (10), 188
(93)
N
N
Me
Me
1H: 2.60 (s, 3 H, CH3), 3.79 (s, 3 H, NCH3), 3.94 (s, 3 H, OCH3),
7.43–7.49 (m, 3 H), 8.05–8.12 (m, 3 H)
CO2Me
193–194
(EtOH)
13C: 14.1, 28.4, 52.5, 114.1, 126.5, 126.9, 128.8, 128.9, 138.3,
149.2, 150.0, 157.0, 165.5
N
62
MS: 282 (18) [M+ + 1], 281 (100) [M+], 251 (10), 250 (78), 222
(45), 204 (35), 201 (11), 183 (11), 181 (55), 77 (78)
N
N
Ph
Me
1H: 2.52 (s, 3 H, CH3), 3.66 (s, 3 H, NCH3), 3.79 (s, 3 H, NCH3),
3.92 (s, 3 H, OCH3), 7.34 (s, 1 H)
CO2Me
Me
155–156
(EtOH)
13C: 23.0, 29.9, 33.9, 52.8, 116.7, 120.7, 120.9, 145.7, 151.2, 164.4,
171.7
N
78
MS: 252 (13) [M+ + 1], 251 (100) [M+], 221 (10), 220 (70), 193
(12), 192 (55), 190 (31), 181 (88), 134 (11), 131 (17)
N
N
Me
Me
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

2754
V. O. Iaroshenko et al.
PAPER
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15 (continued)
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
1H: 2.34 (s, 3 H, CH3), 3.71 (s, 3 H, NCH3), 3.81 (s, 3 H, NCH3),
3.96 (s, 3 H, OCH3), 7.27 (d, J = 7.8, 2 H), 7.89 (s, 1 H), 7.93 (d, J =
7.8, 2 H)
CO2Me
Me
175–177
(EtOH)
N
11h
81
13C: 24.1, 31.2, 34.0, 53.3, 113.6, 118.5, 120.2, 127.2 128.0, 130.0,
137.1, 146.1, 152.4, 169.7, 173.9
S
N
N
Tol-p
MS: 328 (13) [M+ + 1], 327 (100) [M+], 301 (13), 296 (16), 293
(22), 270 (14), 269 (19), 268 (41), 236 (50), 192 (25), 91 (34)
Me
1H: 2.59 (s, 3 H, CH3), 3.71 (s, 3 H, NCH3), 7.47 (s, 1 H), 7.29–7.41
(m, 3 H), 7.52–7.67 (m, 5 H), 8.11–8.15 (m, 2 H)
13C: 14.5, 29.0, 114.7, 127.3, 126.0, 128.8, 129.9, 132.0, 134.2,
141.1, 149.5, 159.1
Ph
N
N
189–191
(EtOH)
12a
12b
12c
12d
43
Me
N
MS: 300 (23) [M+ + 1], 299 (100) [M+], 284 (33), 224 (11), 223
(93), 207 (11), 208 (67), 77 (97)
Ph
Me
1H: 3.35 (s, 3 H, CH3), 3.83 (s, 3 H, CH3), 7.38–7.49 (m, 3 H), 7.53–
7.60 (m, 6 H), 8.11–8.15 (m, 2 H)
Ph
N
Me
N
13C: 29.9, 33.7, 117.2, 122.5, 126.6, 128.4, 128.6, 128.7, 128.8,
129.4, 132.9, 135.5, 138.3, 145.6, 149.7, 172.2
173–175
(EtOH)
72
S
MS: 332 (17) [M+ + 1], 331 (100) [M+], 320 (11), 298 (13), 297
(62), 268 (46), 267 (11), 254 (79), 241 (11), 221 (89), 212 (23), 211
(67), 173 (11), 170 (15), 77 (70)
N
Ph
Me
1H: 2.07 [br s, 4 H, (CH2)2], 3.61 [br s, 4 H, N(CH2)2], 7.39–7.62 (m,
7 H), 7.75 (d, J = 7.2, 2 H), 8.11 (d, J = 7.2, 2 H)
Ph
211–212
(i-PrOH)
13C: 26.1, 49.1, 111.1, 121.9, 126.7, 127.4, 127.1, 128.2, 128.5,
128.7, 137.5, 138.7, 142.3, 153.7, 164.7, 170.9
65
S
N
MS: 358 (27) [M+ + 1], 357 (100) [M+], 329 (36), 328 (17), 303
(13), 302 (56), 287 (11), 261 (11), 260 (23), 259 (12)
N
N
Ph
1H: 1.66 [br s, 6 H, (CH2)3], 3.65 (br s, 4 H), 7.40–7.63 (m, 7 H),
7.78 (d, J = 7.2, 2 H), 8.15 (d, J = 7.2, 2 H)
Ph
13C: 23.0, 24.3, 48.5, 111.5, 121.2, 126.2, 126.9, 127.9, 128.0,
128.57, 128.62, 137.9, 138.8, 142.5, 153.9, 164.8, 169.1
MS: 372 (30) [M+ + 1], 371 (100) [M+], 343 (11), 342 (37), 328
(14), 317 (12), 316 (31), 315 (35), 302 (20), 289 (12), 288 (15), 287
(14), 261 (11), 260 (22), 259 (11)
168–170
(i-PrOH)
60
S
N
N
N
Ph
1H: 3.67 [br s, 4 H, N(CH2)2], 3.80 [br s, 4 H, O(CH2)2], 7.42–7.68
(m, 7 H), 7.71 (d, J = 7.2, 2 H), 8.21 (d, J = 7.2, 2 H)
13C: 48.7, 65.3, 111.1, 121.6, 126.0, 126.5, 128.0, 128.2, 128.50,
128.54, 137.1, 138.9, 142.3, 154.2, 165.2, 168.9
Ph
189–190
(i-PrOH)
12e
67
S
MS: 375 (10) [M+ + 2], 374 (32) [M+ + 1], 373 (100) [M+], 372 (13),
328 (11), 317 (25), 316 (88), 315 (18), 302 (11), 289 (10), 288 (11),
287 (23), 261 (19), 260 (28), 259 (13)
O
N
N
N
Ph
CONHNH2
1H: 2.77 (s, 3 H, CH3), 6.07 (br s, 2 H, NH2), 7.41 (t, J = 8.0, 1 H),
7.77 (t, J = 8.0, 1 H), 7.88 (s, 1 H), 8.00 (d, J = 8.0, 1 H), 8.11 (d,
J = 8.0, 1 H), 10.11 (br s, 1 H, NH)
13a
13b
80
93
195–197
234–238
O
N
Me
CONHNH2
N
1H: 2.56 (s, 3 H, 5-CH3), 2.77 (s, 3 H, SCH3), 5.96 (br s, 2 H, NH2),
7.21 (s, 1 H), 7.50 (m, 5 H), 10.00 (br s, 1 H, NH)
MeS
Me
N
N
Me
Ph
CONHNH2
1H: 2.44 (s, 3 H, 5-CH3), 2.67 (s, 3 H, 2-CH3), 3.80 (s, 3 H, NCH3),
6.19 (br s, 2 H, NH2), 7.87 (s, 1 H), 9.99 (br s, 1 H, NH)
N
13c
51
187–189
N
N
Me
Me
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Desazapurine Isosteres
2755
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15 (continued)
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
CONHNH2
Me
N
1H: 2.52 (s, 3 H, CH3), 3.30 (s, 3 H, CH3), 3.69 (s, 3 H, NCH3), 6.01
(br s, 2 H, NH2), 7.30 (s, 1 H), 10.59 (br s, 1 H, NH)
13d
79
215–218
S
N
N
Me
Me
O
CO2H
1H: 2.62 (s, 3 H, CH3), 7.41 (t, J = 8.0, 1 H), 7.61 (t, J = 8.0, 1 H),
7.70 (s, 1 H), 7.80 (d, J = 8.0, 1 H), 7.93 (d, J = 8.0, 1 H), 11.01 (br
s, 1 H, OH)
14a
14b
89
92
211–213
202–203
N
Me
Me
CO2H
1H: 2.64 (s, 3 H, CH3), 7.38 (t, J = 7.8, 1 H), 7.44 (t, J = 7.8, 1 H),
7.59 (d, J = 7.8, 1 H), 7.71 (s, 1 H), 8.09 (d, J = 7.8, 1 H), 10.97 (br
s, 1 H, OH)
S
N
CO2H
1H: 2.55 (s, 3 H, CH3), 2.73 (s, 3 H, SCH3), 7.19 (s, 1 H), 7.40–7.52
(m, 5 H), 10.77 (br s, 1 H, OH)
N
14c
14d
14e
14f
14g
88
83
68
65
87
250–252
243–244
288–290
270–273
213–215
MeS
N
N
Me
Ph
CO2H
1H: 7.40–7.53 (m, 4 H), 7.68–7.73 (m, 2 H), 7.93 (d, J = 7.8, 2 H),
8.00 (s, 1 H), 8.10 (d, J = 7.8, 2 H), 9.00 (s, 1 H), 11.11 (br s, 1 H,
OH)
N
N
N
Ph
Ph
CO2H
1H: 2.57 (s, 3 H, 5-CH3), 2.69 (s, 3 H, 2-CH3), 3.72 (s, 3 H, NCH3),
7.63 (s, 1 H), 11.07 (br s, 1 H, OH)
N
Me
Me
S
N
N
Me
Ph
Me
CO2H
1H: 2.61 (s, 3 H, 5-CH3), 3.81 (s, 3 H, 2-CH3), 7.47–7.53 (m, 3 H),
8.0–8.05 (m, 3 H), 11.01 (br s, 1 H, OH)
N
N
N
Me
CO2H
Me
1H: 2.52 (s, 3 H, CH3), 3.66 (s, 3 H, NCH3), 3.79 (s, 3 H, NCH3),
7.34 (s, 1 H), 10.59 (br s, 1 H, OH).
N
N
N
Me
Me
CO2H
Me
N
1H: 2.32 (s, 3 H, CH3), 3.74 (s, 3 H, NCH3), 3.84 (s, 3 H, NCH3),
7.33 (d, J = 7.8, 2 H), 7.84 (s, 1 H), 8.01 (d, J = 7.8, 2 H), 10.99 (br
s, 1 H, OH)
14h
15a
82
71
237–239
211–213
S
N
N
Tol-p
Me
CONHPh
1H: 2.63 (s, 3 H, CH3), 7.18 (m, 3 H), 7.44 (t, J = 8.0, 1 H), 7.60 (d,
J = 8.0, 2 H), 7.69 (t, J = 8.0, 1 H), 7.88 (s, 1 H), 7.97 (d, J = 8.0, 1
H), 8.12 (d, J = 8.0, 1 H), 10.01 (br s, 1 H, NH)
O
S
N
N
Me
Me
O
1H: 2.58 (s, 3 H, CH3), 3.74 [br s, 4 H, N(CH2)2], 3.88 [br s, 4 H,
O(CH2)2], 7.37 (t, J = 7.8, 1 H), 7.52 (t, J = 7.8, 1 H), 7.59 (d, J =
7.8, 1 H), 7.77 (s, 1 H), 8.32 (d, J = 7.8, 1 H)
O
N
15b
70
190–193
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

2756
V. O. Iaroshenko et al.
PAPER
Table 1 Yields and Characteristic Data for Heteroannulated Pyridines 10–15 (continued)
Cpd
Structure
Yielda (%) Mpb (°C)
1H and 13C NMR (DMSO-d6) d, J (Hz) and MS m/z (%)c
CONEt2
1H: 1.22 (t, J = 7.2, 6 H, 2 CH3), 2.56 (s, 3 H, 5-CH3), 2.68 (s, 3 H,
N
15c
62
69
177–179
222–223
SCH3), 3.58 (q, J = 7.2, 4 H, 2 CH2), 7.24 (s, 1 H), 7.39–7.53 (m, 5
H)
MeS
N
N
Me
Ph
O
N
1H: 2.08 (br s, 4 H, 2 CH2), 3.51 (br s, 4 H, 2 NCH2), 7.52 (m, 4 H),
7.70 (m, 2 H), 8.03 (d, J = 7.8, 2 H), 8.11 (s, 1 H), 8.19 (d, J = 7.8,
2 H), 8.88 (s, 1 H)
15d
N
N
N
Ph
Ph
CONHPh
1H: 2.46 (s, 3 H, 5-CH3), 2.61 (s, 3 H, 2-CH3), 3.88 (s, 3 H, NCH3),
7.21 (m, 3 H), 7.60 (d, J = 8.0, 2 H), 7.82 (s, 1 H)
N
15e
15f
15g
15h
64
58
60
65
254–255
217–219
234–236
188–190
Me
Me
S
N
N
Me
Me
CONEt2
1H: 1.26 (t, J = 7.2, 6 H, 2 CH3), 2.55 (s, 3 H, CH3), 3.63 (q, 4 H.
J = 7.2 Hz, 2 NCH2), 3.70 (s, 3 H, NCH3), 7.55 (m, 3 H), 8.00–8.10
(m, 3 H)
N
N
N
Ph
Me
CONHPh
Me
1H: 2.50 (s, 3 H, CH3), 3.61 (s, 3 H, NCH3), 3.73 (s, 3 H, NCH3),
7.24 (m, 3 H), 7.68 (d, J = 8.0, 2 H), 7.74 (s, 1 H)
N
N
N
Me
Me
CONEt2
Me
N
1H: 1.26 (t, J = 7.2, 6 H, 2 CH3), 2.30 (s, 3 H, CH3), 3.65 (q, J = 7.2,
4 H, 2 NCH2), 3.71 (s, 3 H, NCH3), 3.81 (s, 3 H, NCH3), 7.30 (d,
J = 7.8, 2 H), 7.80 (s, 1 H), 8.01 (d, J = 7.8, 2 H)
S
N
N
Tol-p
Me
a Yields refer to pure isolated product.
b Melting points are uncorrected.
c Satisfactory microanalysis obtained: C 0.33; H 0.25; N 0.20.
All solvents were purified and dried by standard methods. NMR
spectra were recorded on a Jeol JNM-LA 400, Varian VXR-300 or
Varian Mercury-400, Bruker 600 spectrometer: 1H and 13C signals
(300, 400 and 100 MHz, respectively) were recorded with TMS as
an internal standard; 19F (282.2 and 376.2 MHz) with CFCl3 as in-
ternal standard. IR spectra were recorded on a Perkin Elmer FT IR
1600 spectrophotometer for samples in KBr discs. Mass spectra
were obtained on a Hewlett-Packard HP GC/MS 5890/5972 instru-
ment (EI, 70 eV) by GC inlet or on a MX-1321 instrument (EI, 70
eV) by direct inlet. Elemental analyses were carried out at the
Microanalytical laboratory of the Kiev State University. Column
chromatography was performed on silica gel (63–200 mesh, Merck).
Silica gel Merck 60F254 plates were used for TLC.
Heteroannulated Pyridines via Curtius Rearrangement from
the Corresponding Azides; General Procedure
To a boiling soln of AcOH (30 mL) and H2O (2 mL) (oil bath temp
~145 °C) was added dropwise very slowly through the long con-
denser a mixture of dielectrophile (1 mmol) and the corresponding
azide (3 mmol) in anhyd DMF (40 mL). When the addition was
completed, the mixture was refluxed for a further 3 h. The solvent
was evaporated and the residue was subjected to column chroma-
tography (silica gel), or recrystallized from an appropriate solvent.
It is recommended that the ratio of azide/electrophile 1:3 be use to
obtain an almost quantitative yield of 1-desazapurine.
Heteroannulated Pyridines in Methanol Under Inert Atmo-
sphere; General Procedure
The pyridine synthesis was performed according to one of the fol-
lowing procedures.
The mixture of aminoimidazoles (2 mmol) and dielectrophile (2.2
mmol) in abs MeOH with PTSA (cat.) was heated under reflux in
inert atmosphere for 2–3 h. The solvent was evaporated under re-
duced pressure. The material formed was recrystallized from an ap-
propriate solvent or subjected to column chromatography (silica
gel).
Heteroannulated Pyridines in Acetic Acid; General Procedure
The initial aminoheterocycle (2 mmol) and dielectrophile (2 mmol)
were dissolved in AcOH (25 mL) and heated under reflux for 2 h.
This soln was evaporated under reduced pressure, treated with H2O,
filtered, dried in air, and recrystallized from an appropriate solvent
or subjected to column chromatography (silica gel).
Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Desazapurine Isosteres
2757
Hydrazides 13; General Procedure
13C NMR (DMSO-d6): d = 24.5, 62.1, 70.8, 73.4, 85.0, 88.5, 111.0,
The corresponding compound 11 (1 mmol) and 60% hydrazine hy-
drate (0.5 mL) were dissolved in EtOH (20 mL) and heated under
reflux for 2 h. The soln was left overnight at 0 °C; a precipitate
formed which was filtered, washed once with cold EtOH, and dried
under reduced pressure.
112.9, 122.2, 132.5, 132.51, 145.2, 150.3, 173.8.
1-(2,3-O-Isopropylidene-b-D-ribofuranosyl)-6-methyl-1H-pyra-
zolo[3,4-b]pyridine-4-carbohydrazide (18b)
Compound 17 (2 mmol) and 60% hydrazine hydrate (0.5 mL) were
dissolved in MeOH (15 mL) and the mixture was stirred intensively
at r.t. overnight. The soln was removed under reduced pressure. The
precipitate was recrystallized (MeOH), washed with cold MeOH (2
×), and dried under reduced pressure to give 18b (0.41 g, 57%) as a
colorless solid; mp 149–152 °C.
1H NMR (DMSO-d6): d = 1.33 (s, 3 H, CH3), 1.63 (s, 3 H, 3-CH3),
2.44 (s, 3 H, CH3), 3.63 (dd, 2J = 12.1 Hz, 3J = 3.1 Hz, 1 H), 3.80
(dd, 2J = 12.1 Hz, 3J = 3.1 Hz, 1 H), 4.50 (br s, 1 H), 5.17 (dd, 3J =
5.7 Hz, 3J = 1.5 Hz, 1 H), 5.27 (dd, 3J = 5.4 Hz, 3J = 3.0 Hz, 1 H),
5.97 (s, 2 H, NH2), 6.71 (d, 3J = 2.8 Hz, 1 H), 7.78 (s, 1 H), 8.35 (s,
1 H), 9.97 (s, 1 H, NH).
Acids 14; General Procedure
The corresponding compound 11 (1 mmol) and NaOH (5 mmol)
were dissolved in MeOH (20 mL) and heated under reflux for 2 h.
Then the soln was left overnight at 0 °C; the thus formed precipitate
was filtered and dried in air. The salt was dissolved in H2O (20 mL),
then 1 M HCl was added slowly dropwise with intensive stirring.
The thus formed precipitate was filtered and dried under reduced
pressure.
Acid Chlorides from Acids 14; General Procedure
A mixture of 14 (20 mmol) and SOCl2 (40 mmol) was heated in an-
hyd toluene under reflux for 3 h. Then the solvent was removed un-
der reduced pressure and the residue was dried.
13C NMR (DMSO-d6): d = 25.1, 25.3, 27.0, 53.0, 63.2, 81.5, 85.9,
89.0, 91.4, 112.0, 113.3, 113.9, 114.5, 132.7, 133.3, 148.7, 159.9,
181.0.
Amides 15; General Procedure
6-Methyl-1-(b-D-ribofuranosyl)-1H-pyrazolo[3,4-b]pyridine-4-
carbohydrazide (18c)
Prepared according to the general procedure, then recrystallized
The corresponding acid chloride (1 mmol) and amine (2 mmol) in
anhyd 1,4-dioxane (15 mL) were heated under reflux for 2–3 h. The
mixture was poured into H2O (80 mL). The precipitate formed was
filtered, washed with H2O (2 ×), dried in air, and recrystallized from
an appropriate solvent.
from MeOH.
Colorless solid; yield: 0.20 g (61%); mp 230–231 °C (MeOH).
1H NMR (DMSO-d6): d = 2.57 (s, 3 H, CH3), 3.55 (m, 2 H), 4.00 (q,
Methyl 1-(2,3-O-Isopropylidene-b-D-ribofuranosyl)-6-methyl-
1H-pyrazolo[3,4-b]pyridine-4-carboxylate (17)
3
3J = 4.4 Hz, 1 H), 4.41 (br s, 1 H), 4.67 (d, J = 4.4 Hz, 2 H), 5.21
(br s, 1 H, OH), 5.33 (d, 3J = 5.7 Hz, OH, 1 H), 5.55 (s, 2 H, NH2),
6.77 (d, 3J = 4.4 Hz, 1 H), 8.14 (s, 1 H, CH), 8.77 (s, 1 H, CH), 10.00
(s, 1 H, NH).
13C NMR (DMSO-d6): d = 25.9, 61.9, 71.7, 73.9, 87.0, 89.7, 110.0,
111.9, 122.2, 128.7, 132.33, 145.9, 150.7, 183.7.
A mixture of iso-AIRs 16 (2 mmol) and 1,3-dielectrophile 2 (R =
Me) (2.1 mmol) in DMF (15 mL) under an inert atmosphere was
stirred at 135 °C for 18 h. The mixture was concentrated under re-
duced pressure and the dark material was purified by column chro-
matography (silica gel) to give 17 (0.45 g, 62%) as a colorless solid;
Rf = 0.50 (hexane–EtOAc, 3:1).
1H NMR (CDCl3): d = 1.38 (s, 3 H, CH3), 1.65 (s, 3 H, 3-CH3), 2.39
(s, 3 H, CH3), 3.68 (dd, 2J = 12.8 Hz, 3J = 3.2 Hz, 1 H), 3.86 (dd,
2J = 12.8 Hz, 3J = 2.7 Hz, 1 H), 4.11 (s, 3 H, CH3), 4.53 (br s, 1 H),
5.11 (dd, 3J = 5.9 Hz, 3J = 1.6 Hz, 1 H), 5.27 (dd, 3J = 5.5 Hz, 3J =
2.8 Hz, 1 H), 6.82 (d, 3J = 2.8 Hz, 1 H), 7.78 (s, 1 H), 8.35 (s, 1 H).
13C NMR (CDCl3): d = 25.0, 25.2, 27.2, 53.3, 63.8, 81.9, 85.0, 88.0,
91.8, 110.8, 112.7, 113.7, 113.8, 132.8, 134.1, 148.2, 150.3, 165.9.
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Cleavage of 2,2-Propylidene Protection Group; Synthesis of
Compounds 18a,c; General Procedure
The protected substrate (1 mmol) was dissolved in TFA–H2O (9:1,
10–15 mL) and the mixture was stirred vigorously at r.t. for 60 min
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1H NMR (DMSO-d6): d = 2.44 (s, 3 H, CH3), 3.49 (m, 1 H), 3.63
(m, 1 H), 4.02 (q, 3J = 4.7 Hz, 1 H), 4.34 (br s, 1 H), 4.79 (d, 3J =
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Synthesis 2010, No. 16, 2749–2758 © Thieme Stuttgart · New York

2758
V. O. Iaroshenko et al.
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