Molecules 2011, 16
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3.2.4.1. Synthesis of 12a-b, 13a-b
To a solution of compound 3 (2.92 g, 0.01 mol) or 4 (3.39 g, 0.01 mol) in 1,4-dioxane (25 mL) and
dimethylformamide (10 mL) containing triethylamine (1.00 mL), either malononitrile (0.66 g,
0.01 mol) or ethyl cyanoacetate (1.13 g, 0.01 mol) was added. The reaction mixture, in each case, was
heated under reflux for 5 h, then cooled and neutralized by pouring onto ice/water mixture containing
few drops of hydrochloric acid. The solid product formed, in each case, was filtered off and
crystallized from 1,4-dioxane/dimethylformamide mixture.
4,6-Diamino-1-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic
acid ethyl ester (12a): Brown crystals, m.p. 276-280 °C, yield: 2.36 g (66%); Anal. For C17H18N4O3S
(358.41), (% Calcd./Found): 56.97/57.00 (C), 5.06/5.18 (H), 15.63/15.57 (N), 8.95/9.10 (S); IR (ν, cm−1):
3400-3188 (2NH2), 3083-3002 (CH aromatic), 2932-2852 (CH3, CH2), 2209 (CN), 1673, 1630 (2C=O),
1543, 1461 (C=C); 1H-NMR (δ, ppm): 1.12 (t, J = 7.65 Hz, 3H, ester CH3), 1.72-2.85 (m, 8H, cyclohexene
4CH2), 3.30-3.34 (s, 2H, NH2), 3.82 (s, 2H, NH2), 3.05 (q, J = 7.65 Hz, 2H, ester CH2), 7.92 (s, 1H, pyridine
C5-H); MS m/z (%): 357 [M+–1] (12.37), 356 [M+–2] (18.51), 178 (100.00), 150 (99.10).
4-Amino-1-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-6-hydroxy-2-oxo-1,2-dihydropyridine-3-
carboxylic acid ethyl ester (12b): Pale yellow crystals, m.p. 268-270 °C, yield: 2.59 g (72%); Anal. For
C17H17N3O4S (359.40), (% Calcd./Found): 56.81/57.01 (C), 4.77/4.40 (H), 11.69/11.82 (N), 8.92/9.20
(S); IR (ν, cm−1): 3740-3191 (OH, NH2), 3081 (CH aromatic), 2932-2852 (CH3, CH2), 2208 (CN),
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1676, 1635 (2C=O), 1546, 1460 (C=C); H-NMR (δ, ppm): 1.14 (t, J = 7.50 Hz, 3H, ester CH3),
1.75-2.89 (m, 8H, cyclohexene 4CH2), 3.85 (s, 2H, NH2), 4.07 (q, J = 7.50 Hz, 2H, ester CH2), 6.90 (s,
1H, pyridine C5-H), 11.76 (s, 1H, OH) ; MS m/z (%): 360 [M++1] (0.11), 359 [M+] (0.09), 178
(100.00), 150 (76.57).
4,6-Diamino-1-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic
acid phenylamide (13a): Yellowish white crystals, m.p. 210-212 °C, yield: 2.84 g (70%); Anal. For
C21H19N5O2S (405.47), (% Calcd./Found): 62.21/61.91 (C), 4.72/4.92 (H), 17.27/17.00 (N), 7.91/8.10
(S); IR (ν, cm−1): 3400-3282 (resonating OH, NH, 2NH2), 3081 (CH aromatic), 2932 (CH2
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cyclohexene), 2213 (CN), 1663, 1600, (2C=O) 1544,1442 (C=C); H-NMR (δ, ppm): 1.72-2.94 (m,
8H, cyclohexene 4CH2), 3.44 (s, 2H, NH2), 3.64 (s, 2H, NH2), 6.92 (s, 1H, pyridine C5-H), 7.27-7.56 (m,
5H, C6H5), 10.18 (s, 1H, NH), 11.77 (s, 1H, resonating OH); MS m/z (%): 405 [M+], 407 [M++2]
(41.83), 405 [M+] (42.89), 54 (100.00).
4-Amino-1-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-6-hydroxy-2-oxo-1,2-dihydropyridine-3-
carboxylic acid phenylamide (13b): Pale yellow crystals, m.p. 135-138 °C, yield: 2.48 g (61%); Anal.
For C21H18N4O3S (406.46), (% Calcd./Found): 62.05/61.72 (C), 4.46/4.72 (H), 13.78/13.40 (N),
7.89/8.21 (S); IR (ν, cm−1): 3426-3221 (OH, NH, NH2), 3082 (CH aromatic), 2932-2848 (CH2
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cyclohexene), 2202 (CN), 1662, 1613, (2C=O) 1536,1441 (C=C); H-NMR (δ, ppm): 1.70-2.59 (m,
8H, cyclohexene 4CH2), 3.68 (s, 2H, NH2), 6.90 (s, 1H, pyridine C5-H), 7.03-7.61 (m, 5H, C6H5),
10.13-10.17 (s, 1H, NH), 11.75 (s, 1H, OH).