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I. Pevet et al. / Bioorg. Med. Chem. 19 (2011) 2517–2528
4.1.9.10.
3-Amino-4-methyl-6-trifluoromethyl-thieno[2,3-
4.1.9.15. 3-Amino-6-(2-dimethylamino-ethylamino)-4-phenyl-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene)-hydrazide (21). The product was prepared
according to the general procedure A and led to 591 mg (64%) of
a yellow solid; mp 197–199 °C. 1H NMR (300 MHz, DMSO-d6) d
10.70 (s, 1H, NH), 8.04 (s, 1H), 7.54 (m, 3H), 7.43 (m, 2H), 7.14 (t,
1H, NH), 6.91 (t, 1H), 6.55 (dd, 1H), 6.32 (s, 1H), 6.11 (dd, 1H),
6.2–5.9 (br s, 2H, NH2), 3.85 (s, 3H), 3.44 (q, 2H), 2.44 (t, 2H),
b]pyridine-2-carboxylic acid (3-methyl-3H-imidazol-4-yl-meth-
ylene)-hydrazide (16). The product was prepared according to
the general procedure A and gave 336 mg (44%) of a yellow solid;
mp >230 °C. 1H NMR (400 MHz, DMSO-d6) d 13.20 (s, 1H, OH),
11.45 (br s, 1H, NH), 8.15 (br s, 1H), 7.80 (s, 1H), 7.75 (s, 1H),
7.40 (s, 1H), 7.10 (br s, 2H, NH2), 6.60 (s, 1H), 3.90 (s, 3H), 2.70
(s, 3H). IR (neat)
m 3640, 3260, 1690, 1625, 1347, 1128. Anal. Calcd
for C15H13F3N6OS: C, 46.36; H, 3.43; N, 19.08; S, 7.28. Found: C,
2.20 (s, 6H). IR (neat) m 3469, 3394, 3275, 3020, 2700, 1615,
46.49; H, 3.52; N, 18.78; S, 7.28. HRMS (ESI): calcd for
C
1589. Anal. Calcd for C24H27N7OS: C, 62.45; H, 5.90; N, 21.24; S,
6.95. Found: C, 62.21; H, 5.77; N, 20.93; S, 6.66. HRMS (ESI): calcd
for C24H28N7OS [M+H]+ 462.2076, found 462.2095.
15H14F3N6OS [M+H]+ 383.0902, found 383.0914.
4.1.9.11. 3-Amino-6-(2-dimethylamino-ethylamino)-4-methyl-
thieno[2,3-b]pyridine-2-carboxylic acid naphthalen-1-yl-meth-
ylene-hydrazide (17). The product was prepared according to
the general procedure A and afforded 295 mg (33%) of a yellow
solid. 1H NMR (400 MHz, DMSO-d6) d 11.13 (br s, 1H, NH), 8.90
(s, 1H), 8.45 (m, 1H), 8.14 (d, 1H), 8.02 (d, 2H), 7.7–7.6 (m, 3H),
7.25 (m, 2H, NH2), 6.95 (t, 1H, NH), 6.30 (s, 1H), 3.40 (q, 2H),
4.1.9.16. 3-Amino-4-benzyl-6-(2-dimethylamino-ethylamino)-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene)-hydrazide (22). The product was prepared
according to the general procedure A and afforded 713 mg (75%)
of a yellow powder; mp 196–201 °C. 1H NMR (400 MHz, DMSO-
d6) d 10.70 (s, 1H, NH), 8.05 (br s, 1H), 7.35 (t, 2H), 7.28 (t, 1H),
7.25 (d, 2H), 7.10 (br s, 2H, NH2), 7.00 (t, 1H, NH), 6.91 (t, 1H),
6.52 (m, 1H), 6.11 (t, 1H), 6.01 (s, 1H), 4.37 (s, 2H), 3.85 (s, 3H),
2.59 (s, 3H), 2.42 (t, 2H), 2.19 (s, 6H). IR (neat)
m 3487, 3407,
3292, 1627, 1602, 1571. Anal. Calcd for C24H26N6OS: C, 64.55;
H, 5.87; N, 18.82; S, 7.18. Found C, 64.40; H, 5.95; N, 18.24; S,
7.01. HRMS (ESI): calcd for C24H27N6OS [M+H]+ 447.1967, found
447.1951.
3.35 (q, 2H), 2.37 (t, 2H), 2.14 (s, 6H). IR (neat)
m 3540, 2430,
1612, 1580. Anal. Calcd for C25H29N7OS: C, 63.13; H, 6.15; N,
20.62; S, 6.74. Found: C, 62.97; H, 6.11; N, 20.50; S, 6.57. HRMS
(ESI): calcd for C25H30N7OS [M+H]+ 476.2233, found 476.2244.
4.1.9.12. 3-Amino-6-(2-dimethylamino-ethylamino)-4-methyl-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene)-hydrazide (18). The product was prepared
according to the general procedure A and yielded 711 mg (89%)
of a yellow solid; mp 185–188 °C. 1H NMR (400 MHz, DMSO-d6)
d 10.68 (s, 1H, NH), 7.12 (br s, 1H), 7.12 (m, 2H, NH2), 6.92 (dd,
1H), 6.89 (t, 1H, NH), 6.52 (m, 1H), 6.27 (s, 1H), 6.11 (dd, 1H),
3.85 (s, 3H), 3.38 (q, 2H), 2.57 (s, 3H), 2.41 (t, 2H), 2.18 (s, 6H). IR
4.1.9.17. 3-Amino-6-(2-dimethylamino-ethylamino)-4-propyl-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene)-hydrazide (23). The product was prepared
according to the general procedure A and yielded 522 mg (61%)
of a yellow powder; mp 172–175 °C. 1H NMR (300 MHz, DMSO-
d6) d 10.50 (s, 1H, NH), 8.09 (s, 1H), 7.01 (br s, 2H, NH2), 6.89 (t,
1H), 6.74 (t, 1H, NH), 6.50 (m, 1H), 6.30 (s, 1H), 6.10 (dd, 1H),
3.86 (s, 3H), 3.39 (q, 2H), 2.89 (dd, 2H), 2.44 (t, 2H), 2.20 (s, 6H),
(neat)
m 3468, 3404, 3286, 1626, 1597. Anal. Calcd for C19H25N7OS:
1.69 (m, 2H), 0.99 (t, 3H). IR (neat)
m 3492, 3315, 3239, 3172,
C, 57.12; H, 6.31; N, 24.54; S, 8.03. Found C, 57.04; H, 6.43; N,
2647, 1617, 1604, 1581, 1523. Anal. Calcd for C21H29N7OS: C,
24.01; S, 7.92. HRMS (ESI) calcd for
402.2076, found 402.2093.
C
19H26N7OS [M+H]+
58.99; H, 6.84; N, 22.93; S, 7.50. Found: C, 58.90; H, 6.82; N,
22.88; S, 7.12. HRMS (ESI): calcd for
428.2233, found 428.2250.
C
21H30N7OS [M+H]+
4.1.9.13. 3-Amino-6-(2-dimethylamino-ethylamino)-4-phenyl-
thieno[2,3-b]pyridine-2-carboxylic acid naphthalen-1-yl-meth-
ylene-hydrazide hydrochloride (19). The product was prepared
according to the general procedure A and led to 963 mg (95%) of
a yellow solid; mp 215–217 °C. 1H NMR (400 MHz, DMSO-d6) d
11.25 (s, 1H, NH), 8.90 (s, 1H), 8.43 (d, 1H), 8.18 (d, 1H), 8.05 (d,
2H), 7.72–7.60 (m, 3H), 7.58 (m, 3H), 7.47 (m, 2H), 7.45 (m, 1H,
NH), 6.38 (s, 1H), 6.30–6.20 (br s, 2H, NH2), 3.62 (q, 2H), 2.90 (m,
4.1.9.18. 3-Amino-6-(2-dimethylamino-ethylamino)-5-phenyl-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene) hydrazide (24). The product was prepared accord-
ing to general procedure B and gave 2.72 g (59%) of a yellow solid,
mp = 220 °C. 1H NMR (400 MHz, DMSO-d6) d 10.80 (m, 1H, NH),
8.05 (m, 1H), 8.00 (s, 1H), 7.6–7.4 (m, 2H, NH2), 7.6–7.4 (m, 5H),
6.95 (br s, 1H), 6.55 (br s, 1H), 6.15 (t, 1H), 6.05 (t, 1H, NH), 3.85
2H), 2.55 (br s, 6H). IR (neat)
m 3480, 3300, 3300, 2459, 1610,
(s, 3H), 3.45 (q, 2H), 2.40 (m, 2H), 2.15 (s, 6H). IR (neat)
m 3460
1589. Anal. Calcd for C29H28N6OSÁ0.50HCl: C, 63.90; H, 5.36; N,
(NH2), 3150, 1616, 1600. Anal. Calcd for C24H27N7OS: C, 62.45; H,
15.42; S, 5.88; Cl, 6.50. Found: C, 65.90; H, 5.44; N, 15.75; S,
5.90; N, 21.24; S, 6.95. Found: C, 61.92; H, 5.78; N, 20.76; S, 6.58.
C
29H29N6OS [M+H]+
HRMS (ESI): calcd for
462.2077.
C
24H28N7OS [M+H]+ 462.2076, found
6.10; Cl, 2.91. HRMS (ESI): calcd for
509.2124, found 509.2109.
4.1.9.14. 3-Amino-6-(2-dimethylamino-ethylamino)-4-phenyl-
thieno[2,3-b]pyridine-2-carboxylic acid (3-methyl-3H-imida-
zol-4-yl-methylene)-hydrazide hydrochloride (20). The product
was prepared according to the general procedure A and gave
637 mg (71%) of a yellow powder; mp 210–214 °C. 1H NMR
(400 MHz, DMSO-d6) d 8.10 (m, 1H), 7.78 (s, 1H), 7.58 (d, 2H),
7.58 (t, 1H), 7.45 (m, 2H), 7.38 (s, 1H), 6.30 (s, 1H), 6.20 (m, 2H),
4.1.9.19. 3-Amino-5-benzyl-6-(2-dimethylamino-ethylamino)-
thieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-
yl-methylene) hydrazide (25). The product was prepared accord-
ing to general procedure A and gave 751 mg (79%) of a yellow pow-
der, mp = 192 °C. 1H NMR (400 MHz, DMSO-d6) d 10.70 (m, 1H,
NH), 8.05 (m, 1H), 7.95 (s, 1H), 7.40 (m, 2H, NH2), 7.35–7.26 (m,
5H), 6.90 (m, 1H), 6.55 (m, 1H), 6.25 (t, 1H, NH), 6.10 (m, 1H),
3.90 (s, 2H), 3.85 (s, 3H), 3.40 (q, 2H), 2.40 (t, 2H), 2.10 (s, 6H). IR
3.90 (s, 3H), 3.70 (q, 2H), 3.20 (m, 2H), 2.75 (br s, 6H). IR (neat)
m
3500, 3400, 3300, 1589, 1589, 1620, 1605. Anal. Calcd for
(neat)
m 3340 (NH), 3150, 1614 (C@O), 1596 (C@N). Anal. Calcd
C
23H26N8OSÁ0.9HCl: C, 55.76; H, 5.47; N, 22.62; S, 6.47; Cl, 6.44.
for C25H29N7OS: C, 63.13; H, 6.15; N, 20.62; S, 6.74. Found: C,
63.03; H, 6.09; N, 20.04; S, 6.92. HRMS (ESI): calcd for C25H30N7OS
[M+H]+ 476.2233 found 476.2240.
Found C, 55.75; H, 5.12; N, 22.70; S, 6.61; Cl, 6.45. HRMS (ESI):
calcd for C23H27N8OS [M+H]+ 463.2029, found 463.2045.