Synthesis of novel pyrazolopyridine and pyridopyrimidine derivatives

Article abstract of DOI:10.1002/jhet.547

2-Amino-6-chloropyridine-3,5-dicarbonitrile was used as an intermediate for synthesis of new pyrazolopyridine, pyridopyrimidine, benzodiazepine, and benzothiazipine derivatives.

Full text of DOI:10.1002/jhet.547

592
Synthesis of Novel Pyrazolopyridine and Pyridopyrimidine
Derivatives
Vol 48
A. M. Soliman*
Department of Chemistry, Faculty of Science, Sohag 82524, Egypt
*E-mail: a_sol2000@yahoo.com
Received December 24, 2009
DOI 10.1002/jhet.547
Published online 7 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
2-Amino-6-chloropyridine-3,5-dicarbonitrile was used as an intermediate for synthesis of new pyrazo-
lopyridine, pyridopyrimidine, benzodiazepine, and benzothiazipine derivatives.
J. Heterocyclic Chem., 48, 592 (2011).
by treating of compound 1 with hydrazine hydrate to yield
compound 4 which in turn was treated with 2 mol of 2,5-
dimethoxytetrahydrofurane to afford compound 5.
INTRODUCTION
Pyridine, pyrazole, and pyrimidine derivatives attracted
organic chemists very much due to their biological
and chemotherapeutic importance. Pyridobenzodiazepine
derivatives [1–3], pyrazolopyridine, and related fused het-
erocycles are of interest as potential bioactive molecules.
They are known to exhibit pharmacological activities such
as CNS depressant [4,5], neuroleptic [6], and turberculostatic
[7]. Pyrazolo[3,4-b] pyridines were reported as antimicrobial
agents [8], inhibitors of glycogen synthesis kinase-3(GSK-3)
[9], and potent antitumor agents [10]. Compounds contain-
ing a fused pyrimidine ring have significant biological activ-
ity, particularly in cancer and virus research [11–15].
The chlorine atom attached with compound 2 can be
easily substituted with nucleophilic reagents including
phenylhydrazine, ethyl mercaptoacetate, ethylglycinate,
o-aminothiophenol, o-phenylenediamine, or ethelenedi-
amine provided the substitution intermediate followed
by intramolecular cyclization to yield pyrazolopyridine,
thienopyridine, pyrolopyridine, and pyridobenzodiazi-
pine derivatives 6–9, respectively.
Similar nucleophilic displacement reactions followed by
intramolecular cyclization were carried out with thiourea,
guanidine, or urea to yield 4-amino-7-(1H-pyrrol-1-yl)-2-thi-
oxo-1,2-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile 10a,
4-amino-2-oxo-7-(1H-pyrrol-1-yl)-1,2-dihydropyrido [2,3-d]
pyrimidine-6-carbonitrile 10b, and 4-amino-2-imino-7-(1H-
pyrrol-1-yl)-1,2-dihydropyrido[2,3-d]pyrimidine-6-car-
bonitrile 10c, respectively, (Scheme 1).
Compound 1 was allowed to react with phenylhydra-
zine, ethyl mercaptoacetate, ethylglycinate, o-aminothio-
phenol, o-phenylenediamine, or ethelenediamine, in
ethanol in presence of TEA to give the corresponding
pyrrazolo pyridine 11, thienopyridine 12a, pyrrolopyri-
dines 12b, pyridobenzothiazepine 13a, pyridobenzodia-
zepine 13b, or pyridothiazepine 14, respectively.
Therefore, in view of these observations and in con-
junction with our previous interest in preparing hetero-
cyclic ring systems [16–21], we wish to report herein
the synthesis of some new heterocyclic compounds con-
taining a pyridine moiety fused with pyrazole, pyrimi-
dine, pyrole, thiophene, and benzodiazepine nuclei.
RESULTS AND DISCUSSION
The key 2-amino-6-chloropyridine-3,5-dicarbonitrile 1
was prepared as reported in literature via acidifying the
condensation mixture of malononitrile with triethyl
orthoformate [22].
The reaction of compound 1 with thiourea, guanidine
or urea gave pyridopyrimidine derivatives 15a–c and
with benzoylhydrazide gave compound 16, (Scheme 2).
A multistep synthesis was required for preparing the pyr-
azolopyridine derivative 5. Treatment of compound 1 with
1 mol of 2,5-dimethoxytetrahydrofurane in glacial acetic
acid yielded compound 2 which in turn was allowed to
react with hydrazine hydrate to give compound 3. On treat-
ing compound 3 with another mole of 2,5-dimethoxytetra-
hydrofurane gave compound 5. Otherwise the structure of
compound 5 was proved when synthesized via another rout
EXPERIMENTAL
All melting points were determined on a Kofler melting
points apparatus and are uncorrected. IR spectra were obtained
C
V
2011 HeteroCorporation

May 2011
Synthesis of Novel Pyrazolopyridine and Pyridopyrimidine Derivatives
593
Scheme 1
1
on a Shimadzou FT-IR spectrometer. 1H-NMR spectra were
recorded on a Varian Gemini at 200 MHz using TMS as an in-
ternal reference and DMSO-d6 as a solvent. Mass spectra were
obtained on a Shimadzu GCMS-QP1000 mass spectrometer at
70 ev. Elemental analyses were performed on a Perkin-Elmer
CHN-2400C analyzer model.
260–262ꢀC, ir: 3417, 3333 (NH2), 2210 (CN)cmꢁ1; H-NMR:
d 8.85 (s, 1H, pyridine), 7.55 (d, 2H, pyryl-2,5), 6.66 (br, 1H,
NH), 6.37 (d, 2H, pyryl-3,4), 6.10 (br, 2H, NH2). Anal. Calcd.
for C11H8N6: C, 58.92; H, 3.60; N, 37.48. Found: C, 58.68; H,
3.36; N, 37.82.
3,6-Diamino-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
(4). To a solution of 2-amino-6-chloropyridine-3,5-dicarboni-
trile 1 (1.79 g, 0.01 mol) in ethanol (25 mL), hydrazine
hydrate (0.60 mL, 0.011 mol) was added. The mixture was
refluxed for 1 h. The precipitated product that formed on hot
was filtered off, dried, and crystallized from methanol to yield
1.55 g (89%), mp > 300ꢀC, ir; 3441, 3387, 3310 (NH, NH2),
2-Chloro-6-(1H-pyrrol-1-yl)pyridine-3,5-dicarbonitrile (2). A
mixture of compound 1 (1.79 g, 0.01 mol), 2,5-dimethoxytetra-
hydrofuran (1.32 mL, 0.01 mol), and glacial acetic acid (20 mL)
was heated under reflux for 1 h. The reaction mixture was left to
cool, poured onto ice-water. The precipitated solid was filtered
off, washed with water, dried, and crystallized from ethanol,
yield 1.95 g (86%), mp 138–140ꢀC, ir: 2199(CN)cmꢁ1
;
3210, 3138 (NH2), 2207 (CN) cmꢁ1 1H-NMR: d 8.23 (s,
;
1H-NMR: d 8.83 (s, 1H, pyridine), 7.71, 7.61 (d, 2H, pyryl-2,5),
6.50, 6.42 (d,2H, pyryl-3,4). Anal. Calcd. for C11H5ClN4: C,
57.78; H, 2.20; N, 24.50. Found: C, 57.55; H, 1.95; N, 24.75.
3-Amino-6-(1H-pyrrol-1-yl)-1H-pyrazolo[3,4-b]pyridine-
5-carbonitrile (3). To a solution of compound 2 (1.15 g,
0.005 mol) in ethanol (25 mL), hydrazine hydrate (0.30 mL,
0.0055 mol) was added. The reaction mixture was refluxed for
1 h. The precipitated product formed on hot was filtered off,
dried, and crystallized from ethanol to give 0.80 g (71%), mp
1H,pyridine), 7.90 (s, 1H, NH), 6.70 (br, 4H, 2NH2). MS: m/z
(100%): 174 (100%), 119 (23%), 52 (33%). Anal. Calcd. for
C7H6N6: C, 48.27; H, 3.47; N, 48.25. Found: C, 48.55; H,
3.19; N, 48.67.
3,6-Di-1H-pyrrol-1-yl-1H-pyrazolo[3,4-b]pyridine-5-car-
bonitrile (5). Method A. A mixture of compound 3 (0.87 g,
0.0005 mol) and 2,5-dimethoxytetra-hydrofuran (1.32 mL,
0.001 mol) in glacial acetic acid (15 mL) was heated under
reflux for 1 h. The reaction mixture was left to cool, poured
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

594
A. M. Soliman
Vol 48
Scheme 2
onto ice-cold water. The precipitated solid filtered, washed
with water, dried, and crystallized from dioxane to give 1.0 g
Ethyl 3-amino-5-cyano-6-(1H-pyrrol-1-yl)thieno[2,3-b]pyꢀri-
dine-2-carboxylate 7a. Yield 1.3 g (83%), mp 224–226 C
(73%), mp 330ꢀC (charing), ir: 3425 (NH); 2224 (CN) cmꢁ1
.
(ethanol); IR: 3410, 3328 (NH2), 2214 (CN),1720 (CO) cmꢁ1
;
1H-NMR: d 8.20 (s, 1H, pyridine), 7.95 (s,1H,NH), 7.65, 7.25
(d, 4H, 2pyryl-2,5), 6.30, 6.23 (d,4H, 2pyryl-3,4). Anal. Calcd.
for C15H10N6: C, 65.68; H, 3.67; N, 30.64. Found: C, 65.96;
H, 3.32; N, 30.98.
1H-NMR: d 8.23 (s, 1H, pyridine), 7.65 (d, 2H, pyryl-2,5),
7.34 (s, 2H, NH2), 6.42 (d, 2H, pyryl-3,4), 4.28 (q, 2H, CH2),
1.31 (t, 3H, CH3). MS: m/z (100%): 312 (100%), 266 (69%),
167 (13%). Anal. Calcd. for C15H12N4O2S: C, 57.68; H, 3.87;
N, 17.94. Found: C, 57.35; H, 3.52; N, 18.32.
Method B. A mixture of compound 4 (0.56 g, 25 mmol)
and 2,5-dimethoxytetra-hydrofuran (0.66 mL, 0.005 mol) in
glacial acetic acid (15 mL) was heated under reflux for 1 h
and worked up as above.
Ethyl 3-amino-5-cyano-6-(1H-pyrrol-1-yl)-1H-pyrrolo[2,3-
b]pyridine-2-carboxylate 7b. Yield 1.2 g (81%), mp 178–
180ꢀC (dioxane); IR: 3405, 3320, 3240 (NH, NH2), 2212
;
(CN), 1717 (CO) cmꢁ1 1H-NMR: d 8.80–8.60 (m, 2H, pyri-
dine þNH), 7.65, (d, 2H, pyryl-2,5), 6.41 (d, 2H, pyryl-3,4),
4.35–4.00 (m, 4H, CH2 þ NH2), 1.19 (q, 3H, CH3). Anal.
Calcd. for C15H13N5O2: C, 61.01; H, 4.44; N, 23.72. Found:
C, 60.70; H, 4.09; N, 23.99.
3-Imino-2-phenyl-6-(1H-pyrrol-1-yl)-2,3-dihydro-1H-pyra-
zolo[3,4-b] pyridine-5-carbonitrile (6). To a solution of com-
pound 2 (1.15 g, 0.005 mol) in ethanol (25 mL), triethylamine
(0.6 mL, 0.0059 mol), and phenylhydrazine (0.54 mL, 0.005
mol) were added. The mixture was refluxed for 4 h, then left
to cool and the precipitated product was filtered off, dried, and
crystallized from ethanol, yield 1.1 g (73%), mp 250–252ꢀC,
5-Amino-2-(1H-pyrrol-1-yl)pyrido[2,3-b][1,5]benzothiazepine-
3-carbonitrile 8a. Yield 1.35 g (85%), mp 195–197ꢀC (etha-
1
ir: 3428 (NH), 2220 (CN) cmꢁ1; H-NMR: d 8.90 (s, 1H, pyri-
nol); IR: 3416, 3322 (NH2), 2215 (CN) cmꢁ1 1H-NMR: d
;
dine), 8.15 (d, 2H, CHm), 7.69 (d, 2H, pyryl-2,5), 7.53 (d, 2H,
Ho), 7.26 (d, 1H, Hp), 6.55 (m, 2H, 2NH), 6.28 (d, 2H, pyryl-
3,4). Anal. Calcd. for C16H12N6: C, 67.99; H, 4.03; N, 27.98.
Found: C, 67.65; H, 3.72; N, 28.31.
8.73 (s, 1H, pyridine), 7.56 (d, 2H, H7,10), 7.41 (d, 2H, pyryl-
2,5), 7.20 (d, 2H, H8,9), 6.34 (d, 2H, pyryl-3,4), 5.49 (br, 2H,
NH2). Anal. Calcd. for C17H11N5S: C, 64.34; H, 3.49; N,
22.07. Found: C, 64.04; H, 3.15; N, 22.45.
General procedure for preparation of thieno and pyrro-
lopyridine 7a,b and pyridobenzodiazipine derivatives 8a,b,
and 9. An equimolar ratio of compound 2 (1.14 g, 0.005 mol),
triethyamine (0.6 mL, 0.0059 mol) and ethyl mercaptoacetate,
ethylglycinate, o-aminothiophenol, o-phenelyenediamine, or
ethelenediamine (0.005 mol), was heated under reflux in ethanol
(20 mL) for 3 h. Concentrated, left to cool, the obtained solid
product was filtered off, and crystallized from the proper solvent.
5-Amino-2-(1H-pyrrol-1-yl)-11H-pyrido[2,3-b][1,5]benzodia-
zepine-3-carbonitrile 8b. Yield 1.15 g (77%), mp 240–242ꢀC
1
(ethanol); IR: 3355, 3299, 3236 (NH, NH2) cmꢁ1; H-NMR: d
9.50 (br, 1H, NH), 8.66 (s, 1H, pyridine), 7.49 (d, 2H, pyryl-
2,5), 7.04 (d, 2H, H7,10), 6.82 (d, 1H, H8), 6.58 (d, 1H, H9), 6.33
(s, 2H, pyryl-2,5), 5.09 (br, 2H, NH2). MS: m/z (100%): 300
(44%), 134 (100%), 150 (12%). Anal. Calcd. for C17H12N6: C,
67.99; H, 4.03; N, 27.98. Found: C, 67.65; H, 3.72; N, 28.37.
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5-Amino-8-(1H-pyrrol-1-yl)-2,3-dihydro-1H-pyrido[2,3-e][1,4]
diazepine-7-carbonitrile 9. Yield 0.9 g (71%), mp 233–235ꢀC
Ethyl
3,6-diamino-5-cyano-1H-pyrrolo[2,3-b]pyridine-2-
carboxylate 12b. Yield 0.86 g (70%), mp 178–180ꢀC (etha-
nol); ir: 3416, 3380, 3334, 3231 (NH, 2NH2), 2212 (CN),
(ethanol); ir: 3428, 3343, 3264 (NH, NH2), 2215 (CN) cmꢁ1
;
1H-NMR: d 8.62 (s, 1H, pyridine), 7.79 (d, 2H, pyryl-2,5),
6.41 (d, 2H, pyryl-3,4), 6.34 (s, 2H, NH2), 3.75, 3.03 (tr, 4H,
2CH2). Anal. Calcd. for C13H12N6: C, 61.89; H, 4.79; N,
33.31. Found: C, 61.60; H, 4.46; N, 33.69.
1725 (CO) cmꢁ1; H-NMR: d 8.10 (s, 1H, pyridine), 7.74 (br,
1
1H, NH), 7.37 (s, 2H, NH2), 4.20–4.00 (m, 4H, NH2 þ CH2
ester), 1.28–1.23 (t, 3H, CH3 ester). MS: m/z (100%): 245
(17%), 172 (100%). Anal. Calcd. for C11H11N5O2: C, 53.87;
H, 4.52; N, 28.56. Found: C, 53.59; H, 4.22; N, 28.90.
General procedure for preparation of compounds 13a,b
and 14. A solution of compound 1 (0.90 g, 0.005 mol) and
ortho aminothiophenol, benzene-1,2-diamine, or ethylenedia-
mine (0.005 mol) in ethanol (20 mL) was treated with triethyl-
amine (0.6 mL, 0.0059 mol). The reaction mixture was
refluxed for 1 h and 3 h, respectively, then left to cool. The
precipitated solid was filtered off and crystallized from the
proper solvent.
General procedure for preparation of pyrido[2,3-d]py-
rimidine derivatives 10a–c. A mixture of compound 2 (1.14
g, 0.005 mol), sodium carbonate (0.5 g, 0.005 mol) and thio-
ura, urea, or guanidine were refluxed in ethanol for 6 h con-
centrated, left to cool, and then poured onto ice/cold water.
The obtained solid was collected and crystallized from the
proper solvent.
4-Amino-7-(1H-pyrrol-1-yl)-2-thioxo-1,2-dihydropyrido[2,3-
d]pyrimidine-6-carbonitrile 10a. Yield 1.25 g (79%), mp 233–
235ꢀC (dioxane); ir: 3428, 3343, 3264 (NH, NH2), 2215 (CN)
cmꢁ1 1H-NMR: d 9.30 (br, 1H, NH), 8.70 (s, 1H, pyridine),
;
7.66 (d, 2H, pyryl-2,5), 6.25 (d, 2H, pyryl-3,4), 5.95 (s, 2H,
NH2). Anal. Calcd. for C12H8N6S: C, 53.72; H, 3.01; N, 31.32.
Found: C, 53.99; H, 2.78; N, 31.66.
4-Amino-2-oxo-7-(1H-pyrrol-1-yl)-1,2-dihydropyrido[2,3-
d]pyrimidine-6-carbonitrile 10b. Yield 0.86 g (68%), mp
170–172ꢀC (methanol); ir: 3410, 3335, 3245 (2NH, NH2),
;
2228 (CN) cmꢁ1 1H-NMR: d 9.65, 8.76 (br, 2H, 2NH), 8.45
2,5-Diaminopyrido[2,3-b][1,5]benzothiazepine-3-carbonitrile
13a. Yield 0.92 g (69%), mp 270–272ꢀC (methanol); ir: 3422,
3327, 3224 (2NH2), 2216 (CN) cmꢁ1; H-NMR: d 9.25 (s, 1H,
1
pyridine), 7.64–7.20 (m, 8H, arom., 2NH2). Anal. Calcd. for
C13H9N5S: C, 58.41; H, 3.39; N, 26.20. Found: C, 58.10; H,
3.08; N, 26.55.
2,5-Diamino-11H-pyrido[2,3-b][1,5]benzodiazepine-3-carbon-
itrile 13b. Yield 0.79 g (63%), mp 198–200ꢀC (ethanol); ir:
3420, 3341, 3296, 3226 (NH, 2NH2), 2217 (CN) cmꢁ1 1H-
;
NMR: d 8.44 (br, 1H, NH), 8.12 (s, 1H, pyridine), 7.25 (br,
2H, NH2), 7.12 (d, 1H, H7), 6.97 (d, 1H, H10), 6.78 (d, 1H,
H8), 6.58 (d, 1H, H9), 4.92 (br, 2H, NH2). MS: m/z (100%):
250 (45%), 178 (100%), 143 (67%), 89 (47%). Anal. Calcd.
for C13H10N6: C, 62.39; H, 4.03; N, 33.58. Found: C, 62.11;
H, 3.75; N, 33.94.
(s, 1H, pyridine), 7.58 (d, 2H, pyryl-2,5), 6.30 (d, 2H, pyryl-
3,4), 4.90 (s, 2H, NH2). Anal. Calcd. for C12H8N6O: C, 57.14;
H, 3.20; N, 33.32. Found: C, 57.43; H, 2.90; N, 33.70.
4-Amino-2-imino-7-(1H-pyrrol-1-yl)-1,2-dihydropyrido[2,3-
d]pyrimidine-6-carbonitrile 10c. Yield 0.83
233–235ꢀC (ethanol); ir: 3418, 3333, 3254 (NH, NH2), 2215
(CN), 1678 (CO) cmꢁ1 1H-NMR: d 9.15 (br, 1H, NH), 8.57
g (66%), mp
5,8-Diamino-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepine-7-
carbonitrile 14. Yield 0.74 g (73%), mp 213–215ꢀC (metha-
;
(s, 1H, pyridine), 7.56 (d, 2H, pyryl-2,5), 6.15 (d, 2H, pyryl-
3,4), 5.85 (s, 2H, NH2). Anal. Calcd. for C12H9N7: C, 57.37;
H, 3.61; N, 39.02. Found: C, 57.07; H, 3.30; N, 39.39.
nol); ir: 3342, 3215, 3150 (NH, 2NH2), 2209 (CN) cmꢁ1
;
1H-NMR: d 8.03 (s, 1H, pyridine), 7.41, 7.27 (br, 4H, 2NH2),
3.56 (t, 2H, H8), 3.44 (t, 2H, H7). Anal. Calcd. for C9H10N6:
C,53.46; H, 4.98; N, 41.56. Found: C, 53.18; H, 4.70; N,
41.90.
6-Amino-3-imino-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]pyri-
dine-5-carbonitrile 11. A solution of compound 1 (0.90 g,
0.005 mol) in ethanol (25 mL) was treated with phenylhydra-
zine (0.54 mL, 0.005 mol). The reaction mixture was refluxed
for 3 h, then left to cool. The precipitated product was filtered
off, dried, and crystallized from ethanol, yield 0.81 g (65%),
mp 320ꢀC (ethanol); ir: 3428, 3368, 3182 (2NH, NH2), 2223
General procedure for preparation of compounds 15a–c. A
solution of compound 1 (0.90 g, 0.005 mol) and thiourea, gua-
nidine, or urea (0.005 mol) in DMF (20 mL) was refluxed for
3 h then left to cool. The precipitated solid was filtered off
and crystallized from the proper solvent.
1
(CN) cmꢁ1; H-NMR: d 8.54 (s, 1H, pyridine), 7.62–7.46 (m,
4,7-Diamino-2-thioxo-1,2-dihydropyrido[2,3-d]pyrimidine-6-
carbonitrile 15a. Yield 0.85 g (78%), mp > 300ꢀC (DMF); ir:
5H, phenyl), 7.44, 7.34 (s, 2H, 2NH), 7.24 (br, 2H, NH2).
Anal. Calcd. for C13H10N6: C, 62.39; H, 4.03; N, 33.58.
Found: C, 62.70; H, 3.78; N, 33.95.
3440, 3361, 3315 (NH, 2NH2), 2060 (CN) cmꢁ1 1H-NMR:
;
General procedure for preparation of compounds
12a,b. An equimolar ratio of compound 1 (0.90 g, 0.005 mol)
and ethyl mercaptoacetate (0.60 mL, 0.005 mol) in ethanol (20
mL) was treated with triethylamine (0.6 mL, 0.0059 mol). The
reaction mixture was refluxed for 4 h, then left to cool. The
precipitated solid was filtered off and crystallized from the
proper solvent.
d 9.35 (br, 1H, NH), 8.34 (s, 1H, pyridine), 8.06, 7.56 (br, 4H,
2NH2). Anal. Calcd. for C8H6N6S: C,44.03; H, 2.77; N, 38.51.
Found: C, 43.74; H, 2.47; N, 38.89.
4,7-Diamino-2-imino-1,2-dihydropyrido[2,3-d]pyrimidine-6-
carbonitrile 15b. Yield 0.76 g (76%), mp 201–203ꢀC (etha-
nol); ir: 3423, 3332, 3232 (2NH, 2NH2), 2221 (CN) cmꢁ1
;
1H-NMR: d 8.78 (br, 1H, NH), 8.32 (s, 1H, pyridine), 7.87,
4.41 (br, 4H, 4NH2). Anal. Calcd. for C8H7N7: C,47.76; H,
3.51; N, 48.73. Found: C, 47.46; H, 3.22; N, 49.08.
Ethyl 3,6-diamino-5-cyanothieno[2,3-b]pyridine-2-carboxy-
late 12a. Yield 0.9 g (69%), mp 280–282ꢀC (dioxane); ir: 3415,
3328, 3224 (2NH2), 2210 (CN), 1728 (CO) cmꢁ1 1H-NMR:
;
4,7-Diamino-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidine-6-car-
bonitrile 15c. Yield 0.73 g (72%), mp 213–215ꢀC (ethanol); ir:
d 8.63 (s, 1H, pyridine), 7.40, 7.14 (s, 4H, 2NH2), 4.25–4.18 (q,
2H, CH2 ester), 1.28–1.23 (t, 3H, CH3 ester). MS: m/z (100%):
262 (100%), 216 (92%), 144 (18%). Anal. Calcd. for
C11H10N4O2S: C, 50.37; H, 3.84; N, 21.36. Found: C, 50.65; H,
3.55; N, 21.73.
3407, 3352, 3238 (NH, 2NH2), 2212 (CN), 1662 (CO) cmꢁ1
;
1H-NMR: d 8.05 (s, 1H, pyridine), 7.40–7.00 (br, 2NH2).
Anal. Calcd. for C8H6N6O: C,47.53; H, 2.99; N, 41.57. Found:
C, 47.26; H, 2.62; N, 41.94.
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A. M. Soliman
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[8] Goda, F. E.; Abdel-Aziz, A. A. M.; Attef, O. A. Bioorg
Med Chem Lett 2004, 12, 1845.
6-Amino-2-benzoyl-3-imino-2,3-dihydro-1H-pyrazolo[3,4-b]pyr-
idine-5-carbonitrile 16. An equimolar ratio of compound 1
(0.90 g, 0.005 mol) and benzoylhydrazide (0.68 g, 0.005 mol)
in ethanol (20 mL) was treated with triethylamine (0.6 mL,
0.0059 mol). The reaction mixture was refluxed for 3 h, then
left to cool. The precipitated solid was filtered off and crystal-
lized from ethanol. Yield 0.96 g (69%), mp 250–252ꢀC, ir:
[9] Witherington, J.; Bordas, V.; Garland, S. L.; Hickey, D. M.
B.; Lfe, R. J.; Liddle, J.; Saunders, M. D.; Smith, G.; Ward, R. W.
Bioorg Med Chem Lett 2003, 13, 1577.
[10] Lin, R.; Connolly, P. J.; Lu, Y.; Chin, G.; Li, S.; Yu, Y.;
Huang, S.; Li, X.; Emanuel, S. L.; Middleton, S. A.; Gruninger, R. H.;
Adams, M.; Fuentes-Pesquera, A. R.; Greenberger, L. M. Bioorg Med
Chem Lett 2007, 17, 4292.
3434, 3337, 3237 (2NH, NH2), 2216 (CN) cmꢁ1 1H-NMR:
,
d 10.57, 9.45 (br, 2H, 2NH), 8.15 (s, 1H, pyridine), 7.93 (br,
2H, NH2), 7.60–7.10 (m, 5H, arom). Anal. Calcd. for
C14H10N6O: C,60.43; H, 3.62; N, 30.20. Found: C, 60.13; H,
3.33; N, 30.57.
[11] Jones, A. S.; Sayers, J. R.; Walker, R. T.; De Clercq, E. J
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet