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H. Ochiai et al. / Bioorg. Med. Chem. 12 (2004) 4089–4100
1473, 1403, 1385, 1334, 1148; MS (FAB, Pos.) 375
1
1496, 1442, 1405, 1384, 1357, 1282, 978; MS (APCI, Pos.
20 V) 306 (M+H)þ; 1H NMR (300 MHz, DMSO-d6)
10.91 (s, 1H), 8.75 (s, 1H), 8.25 (s, 1H), 7.60 (br s, 1H),
7.10–7.35 (m, 4H), 4.17 (s, 1H), 3.89 (s, 3H), 1.67 (s,
3H); HRMS (EI) calcd for C17H15N5O1 305.1277, found
305.1293.
(M+H)þ; H NMR (300MHz, DMSO-d6) 10.96 (s, 1H),
9.72 (s, 1H), 8.75 (s, 1H), 8.23 (b s, 1H), 7.59 (b s, 1H),
7.27 (t, J ¼ 8:1 Hz, 1H), 7.00–6.92 (m, 2H), 6.87–6.81 (m,
1H), 3.89 (s, 3H), 2.94 (s, 3H), 1.70 (s, 3H); HRMS (EI)
calcd for C16H18N6O3S1 374.1161, found 374.1172.
5.3.14. Methyl 3-{[5-(aminocarbonyl)-1,3-dimethyl-1H-
pyrazolo[3,4-b]pyridin-4-yl]amino}phenylcarbamate (15).
Yield 53%; White powder; TLC Rf 0.41 (CHCl3/MeOH,
10/1); IR (KBr) 3463, 3345, 2204, 2948, 1716, 1666,
1586, 1533, 1501, 1457, 1407, 1386, 1354, 1283, 1250,
1074, 984, 803, 778, 711, 604, 553; MS (APCI, Pos. 20 V)
355 (M+H)þ, 297, 279; 1H NMR (300 MHz, DMSO-d6)
10.99 (s, 1H), 9.62 (s, 1H), 8.73 (s, 1H), 8.21 (br, 1H),
7.56 (br, 1H), 7.23–7.19 (m, 3H), 6.75–6.71 (m, 1H), 3.87
(s, 3H), 3.61 (s, 3H), 1.67 (s, 3H); HRMS (EI) calcd for
C17H18N6O3 354.1440, found 354.1425.
5.3.19.
4-[(2,4-Dimethoxyphenyl)amino]-1,3-dimethyl-
1H-pyrazolo[3,4-b]pyridine-5-carboxamide (21). Yield
64%; White powder; TLC Rf 0.32 (CHCl3/MeOH, 10/1);
IR (KBr) 3364, 3179, 1667, 1616, 1583, 1568, 1518,
1440, 1384, 1211; MS (FAB, Pos.) 342 (M+H)þ, 325; 1H
NMR (300 MHz, DMSO-d6) 10.81 (s, 1H), 8.66 (s, 1H),
8.11 (b s, 1H), 7.42 (b s, 1H), 6.92 (d, J ¼ 8:4 Hz, 1H),
6.69 (d, J ¼ 2:7 Hz, 1H), 6.44 (dd, J ¼ 8:4, 2.7 Hz,
1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.76 (s, 3H), 1.53 (s, 3H);
HRMS (EI) calcd for C17H19N5O3 341.1488, found
341.1498.
5.3.15. 4-[(3-Cyanophenyl)amino]-1,3-dimethyl-1H-pyr-
azolo[3,4-b]pyridine-5-carboxamide (16). Yield 95%;
Beige powder; TLC Rf 0.38 (AcOEt); IR (KBr) 3423,
3350, 3215, 3052, 2240, 1668, 1619, 1593, 1562, 1522,
1482, 1408, 1384, 1358, 1301, 1266, 1146, 977; MS (EI,
Pos.) 306 (M)þ, 289, 260, 246, 233, 218; 1H NMR
(300 MHz, DMSO-d6) 10.83 (s, 1H), 8.76 (s, 1H), 8.23
(br, 1H), 7.60 (br, 1H), 7.56–7.44 (m, 3H), 7.41–7.36 (m,
1H), 3.91 (s, 3H), 1.72 (s, 3H); HRMS (EI) calcd for
C16H14N6O1 306.1229, found 306.1217.
5.3.20. 4-[2,5-Dimethoxyphenyl)amino]-1,3-dimethyl-1H-
pyrazolo[3,4-b]pyridine-5-carboxamide (22). Yield 55%;
Pale yellow powder; TLC Rf 0.32 (CHCl3/MeOH, 10/1);
IR (KBr) 3308, 3170, 1678, 1629, 1560, 1509, 1430,
1225; MS (FAB, Pos.) 342 (M+H)þ, 325; 1H NMR
(300 MHz, DMSO-d6) 11.03 (s, 1H), 8.75 (s, 1H), 8.29 (b
s, 1H), 7.61 (b s, 1H), 7.04 (d, J ¼ 9:0 Hz, 1H), 6.72 (dd,
J ¼ 9:0, 3.0 Hz, 1H), 6.59 (d, J ¼ 3:0 Hz, 1H), 3.91 (s,
3H), 3.78 (s, 3H), 3.59 (s, 3H), 1.66 (s, 3H); HRMS (EI)
calcd for C17H19N5O3 341.1488, found 341.1498.
5.3.16. 4-{[3-(Hydroxymethyl)phenyl]amino}-1,3-dimeth-
yl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide (18). Yield
64%; White powder; TLC Rf 0.65 (CHCl3/MeOH, 9/1);
IR (KBr) 3356, 3189, 1671, 1588, 1525, 1439, 1405,
1385, 1357, 1298, 1273, 1142, 1048, 983; MS (APCI, Pos.
20 V) 312 (M+H)þ; 1H NMR (300 MHz, DMSO-d6)
11.05 (s, 1H), 8.73 (s, 1H), 8.20 (br, 1H), 7.54 (br, 1H),
7.26 (dd, J ¼ 8:0, 8.0 Hz, 1H), 7.08–7.03 (m, 2H), 6.96
(d, J ¼ 8:0 Hz, 1H), 5.16 (t, J ¼ 6:2 Hz, 1H), 4.42 (d,
J ¼ 6:2 Hz, 2H), 3.87 (s, 3H), 1.61 (s, 3H); HRMS (EI)
calcd for C16H17N5O2 311.1382, found 311.1377.
5.3.21.
4-[(3,4-Dimethoxyphenyl)amino]-1,3-dimethyl-
1H-pyrazolo[3,4-b]pyridine-5-carboxamide (23). Yield
23%; White powder; TLC Rf 0.32 (CHCl3/MeOH, 10/1);
IR (KBr) 3429, 3198, 1672, 1616, 1588, 1520, 1246; MS
(FAB, Pos.) 342 (M+H)þ, 325; 1H NMR (300 MHz,
DMSO-d6) 11.12 (s, 1H), 8.70 (s, 1H), 8.17 (b s, 1H),
7.49 (b s, 1H), 6.88 (d, J ¼ 8:4 Hz, 1H), 6.85 (d,
J ¼ 2:4 Hz, 1H), 6.61 (dd, J ¼ 8:4, 2.4 Hz, 1H), 3.86 (s,
3H), 3.73 (s, 3H), 3.69 (s, 3H), 1.59 (s, 3H); HRMS (EI)
calcd for C17H19N5O3 341.1488, found 341.1498.
5.3.22. 4-[3,5-Dimethoxyphenyl)amino]-1,3-dimethyl-1H-
pyrazolo[3,4-b]pyridine-5-carboxamide (24). Yield 17%;
White powder; TLC Rf 0.32 (CHCl3/MeOH, 10/1); IR
(KBr) 3351, 3185, 1672, 1611, 1592, 1565, 1520, 1382,
1158; MS (FAB, Pos.) 342 (M+H)þ, 325; 1H NMR
(300 MHz, DMSO-d6) 10.90 (s, 1H), 8.73 (s, 1H), 8.20 (b
s, 1H), 7.55 (b s, 1H), 6.26 (s, 1H), 6.25 (s, 2H), 3.89 (s,
3H), 3.67 (s, 6H), 1.79 (s, 3H); HRMS (EI) calcd for
C17H19N5O3 341.1488, found 341.1498.
5.3.17. 4-[(3-Acetylphenyl)amino]-1,3-dimethyl-1H-pyr-
azolo[3,4-b]pyridine-5-carboxamide (19). Yield 37%;
Yellow powder; TLC Rf 0.30 (EtOAc); IR (KBr) 3341,
3193, 1662, 1586, 1562, 1523, 1498, 1441, 1403, 1384,
1358, 1314, 1272; MS (EI, Pos.) 323 (M)þ, 306, 291, 264;
1H NMR (300 MHz, DMSO-d6) 11.00 (s, 1H), 8.77 (s,
1H), 8.24 (b s, 1H), 7.70 (d, J ¼ 7:5 Hz, 1H), 7.63 (s,
1H), 7.59 (b s, 1H), 7.46 (t, J ¼ 7:5 Hz, 1H), 7.35 (d,
J ¼ 7:5 Hz, 1H), 3.91 (s, 3H), 2.54 (s, 3H), 1.65 (s, 3H);
HRMS (EI) calcd for C17H17N5O2 323.1382, found
323.1387.
5.3.23.
4-[(2,3-Dimethoxyphenyl)amino]-1,3-dimethyl-
1H-pyrazolo[3,4-b]pyridine-5-carboxamide (25). Yield
65%; Pale yellow powder; TLC Rf 0.32 (CHCl3/MeOH,
10/1); IR (KBr) 3348, 3187, 1679, 1644, 1622, 1589,
1559, 1490, 1480, 1431, 1269, 1093; MS (FAB, Pos.) 342
5.3.18. 4-[(3-Ethynylphenyl)amino]-1,3-dimethyl-1H-pyr-
azolo[3,4-b]pyridine-5-carboxamide (20). Yield 93%;
White powder; TLC Rf 0.22 (CHCl3/MeOH, 9/1); IR
(KBr) 3396, 3291, 3191, 1666, 1613, 1586, 1563, 1523,
1
(M+H)þ, 325; H NMR (300 MHz, DMSO-d6) 11.17 (b
s, 1H), 8.78 (s, 1H), 8.32 (b s, 1H), 7.65 (b s, 1H), 6.96 (t,