SYNTHESIS OF 4- OR 6-SUBSTITUTED INDIRUBIN DERIVATIVES
3131
under reduced pressure, the residue was purified by chromatography on silica gel with
cyclohexane–acetic ether (5:1) and dichloromethane–methanol (100:1) to give 7a.
The method of synthesis of 7b–e and 8a–d was the same.
4-Fluoroindirubin (7a). Yield: 3%; mp > 300 ꢀC; IR (cmꢁ1, KBr): 3224, 1677,
1
1619, 1578, 1466, 1303, 1248, 1139; H NMR (300 MHz, DMSO-d6) d (ppm) 11.17
(1H, s, 10-NH), 11.01 (1H, s, 1-NH), 7.62–7.65 (1H, d, J ¼ 7.7 Hz, 40-H), 7.55–7.61
(1H, m, 60-H), 7.37–7.40 (1H, d, J ¼ 8.0 Hz, 70-H), 7.22–7.29 (1H, m, 6-H),
7.02–7.07 (1H, t, J ¼ 6.9 Hz, 50-H), 6.78–6.87 (1H, m, 5-H), 6.73–6.76 (1H, d,
J ¼ 7.7 Hz, 7-H); 13C NMR (75 MHz, DMSO-d6) d (ppm) 183.2, 171.0, 152.1,
141.9, 138.7, 137.4, 130.8, 130.3, 124.9, 122.4, 120.4, 119.8, 114.0, 109.6, 109.4,
106.3; MS (ESI) m=z: 282 [M]þ. Anal. calcd. for C16H9FN2O2 (%): C, 68.57; H,
3.24; N, 10.00. Found: C, 68.59; N, 17.70.
4-Chloroindirubin (7b). Yield: 49%; mp > 300 ꢀC; IR (cmꢁ1, KBr): 3325,
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1664, 1614, 1585, 1465, 1301, 1240, 1138, 1004; H NMR (300 MHz, DMSO-d6) d
(ppm) 11.25 (1H, s, 10-NH), 10.95 (1H, s, 1–NH), 7.64–7.66 (1H, d, J ¼ 5.7 Hz,
40-H), 7.56–7.60 (1H, t, J ¼ 6.3 Hz, 60-H), 7.35–7.37 (1H, d, J ¼ 6.0 Hz, 70-H),
7.19–7.23 (1H, t, J ¼ 6.0 Hz, 6-H), 7.01–7.07 (2H, m, 5-H, 50-H), 6.83–6.85 (1H, d,
J ¼ 5.1 Hz, 7-H)[9]; 13C NMR (75 MHz, DMSO-d6) d (ppm) 186.3, 170.7, 151.1,
142.7, 137.9, 136.6, 130.0, 129.2, 124.3, 122.8, 121.9, 120.7, 119.2, 113.5, 107.8,
103.3; MS (ESI) m=z: 298[M]þ. Anal. calcd. for C16H9ClN2O2 (%): C, 64.77; H,
3.06; N, 9.44. Found: C, 65.97; N, 10.48.
4-Bromoindirubin (7c). Yield: 8%; mp > 300 ꢀC; IR (cmꢁ1, KBr): 3293, 1671,
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1610, 1583, 1462, 1293, 1199, 1137, 1000; H NMR (300 MHz, DMSO-d6) d (ppm)
11.24 (1H, s, 10-NH), 10.95 (1H, s, 1-NH), 7.67–7.69 (1H, d, J ¼ 7.7 Hz, 40-H),
7.57–7.63 (1H, t, J ¼ 8.0 Hz, 60-H), 7.37–7.37 (1H, d, J ¼ 8.0 Hz, 70-H), 7.20–7.23
(1H, dd, J ¼ 8.2 Hz, 5-H), 7.11–7.16 (1H, t, J ¼ 7.7 Hz, 6-H), 7.05–7.10 (1H, t,
J ¼ 7.4 Hz, 50-H), 6.89–6.92 (1H, dd, J ¼ 7.4 Hz, 7-H); 13C NMR (75 MHz,
DMSO-d6) d (ppm) 186.2, 170.4, 151.2, 142.9, 137.7, 136.8, 129.1, 125.9, 124.4,
122.1, 122.1, 119.4, 119.1, 113.5, 108.3, 104.7; MS (ESI) m=z: 342 [M]þ. Anal. calcd.
for C16H9BrN2O2 (%): C, 56.33; H, 2.66; N, 8.21. Found: C, 57.21; N, 7.87.
4-Trifluoromethylindirubin (7d). Yield: 19%; mp > 300 ꢀC; IR (cmꢁ1, KBr):
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3316, 1672, 1593, 1468, 1310, 1291, 1214, 1111, 1006; H NMR (300 MHz, DMSO-
d6) d (ppm) 11.22 (1H, br, 10-NH), 11.02 (1H, s, 1-NH), 7.54–7.61 (2H, m, 40-H,
60-H), 7.33–7.38 (2H, m, 6-H, 70-H), 7.19–7.21 (1H, d, J ¼ 7.6 Hz, 5-H), 7.00–7.07
(2H, m, 50-H, 7-H); 13C NMR (75 MHz, DMSO-d6) d (ppm) 187.1, 170.6, 152.4,
142.5, 140.2, 138.0, 130.3, 128.9, 125.5, 123.0, 120.5, 119.7, 119.1, 114.3, 113.0,
103.6, 29.8; MS (ESI) m=z: 331 [M]þ. Anal. calcd. for C17H9F3N2O2 (%): C,
61.82; H, 2.75; N, 8.48. Found: C, 61.97; N, 9.15.
4-Nitroindirubin (7e). Yield: 15%; mp > 300 ꢀC; IR (cmꢁ1, KBr): 3364, 1675,
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1593, 1462, 1354, 1289, 1193, 1142; H NMR (300 MHz, DMSO-d6) d (ppm) 11.42
(1H, s, 10-NH), 11.23 (1H, s, 1-NH), 7.57–7.62 (2H, m, 40-H, 60-H), 7.51–7.54 (1H,
dd, J ¼ 6.3 Hz, 70-H), 7.36–7.40 (2H, m, 5-H, 6-H), 7.19–7.21 (1H, dd, J ¼ 5.7 Hz,
7-H), 7.04–7.07 (1H, t, J ¼ 5.4 Hz, 50-H); 13C NMR (75 MHz, DMSO-d6) d (ppm)
188.1, 170.4, 152.4, 145.6, 143.3, 139.9, 138.3, 128.9, 125.7, 123.3, 119.4, 119.4,