Medicinal Chemistry Research
2851.7, 1629.7, 1446.5, 1384.2, 1274.3, 1114.1, 850.9; 1H-
NMR (600 MHz, DMSO-d6): δ 4.40 (d, 2H, Ar-CH), 4.42
(s, 2H, S-CH2), 7. 36–7.43(m, 5H, Ar-H), 7.42 (s, 1H, H-
10), 8.82(s, 1H, NHC=O), 13.64(s, 1H, NH); 13C-NMR
(101 MHz, DMSO-d6) δ 162.34 (C=O), 140.19 (C-1),
136.50 (C-11), 133.96 (C-2), 131.72 (C-6), 129.12, 128.69,
127.81, 127.45, 127.17, 127.01, 126.27, 109.45, 108.88
(Ar-H), 42.34 (NH-CH2), 25.85 (C-3); HRMS (ESI) m/z
C19H15BrFN4OS2 [M-H]-(calcd. 476.986017); purity
(HPLC): 99.12%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(3-bromophenyl)piperazine
(8c): white solid, 0.82 g, yield 38%. mp. 150–151 °C; IR
(KBr, cm−1): 3418.7, 3217.5, 2920.0, 2850.7, 1590.4,
1480.6, 1442.9, 1384.6, 1224.6, 1157.9, 999.9, 938.2,
1
764.3; H-NMR (600 MHz, CDCl3): δ 3.20–3.27(m, 4H,
(neg):
403.953743,
C16H11BrN3OS2
[M-H]-(calcd.
Ar-N(CH2)2), 3.98–4.04(m, 4H, CON(CH2)2), 4.26(s, 2H,
S-CH2), 6.85(m, 1H, Ar-H), 7.00–7.03(m, 1H, Ar-H),
7.05–7.09(m, 1H, Ar-H), 7.11–7.14(m, 1H, Ar-H), 7.23 (s,
1H, H-10); 13C-NMR (101 MHz, DMSO-d6) δ 161.68
(C=O), 152.58 (C-14), 132.17 (C-1), 131.97 (C-2), 131.61
(C-18), 131.23 (C-6), 129.12, 126.28, 123.00, 121.87,
118.26, 114.87, 110.41, 108.96 (Ar-H), 48.74, 48.37 (C-11,
C-12), 46.52, 42.02 (C-10, C-13), 25.92 (C-3); HRMS
(ESI) m/z (neg): 536.906767, C19H15Br2N4OS2 [M-H]-
(calcd. 536.905951); purity (HPLC): 99.62%.
403.953240); purity (HPLC): 98.68%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(2-methylphenyl)piperazine
(7f): white solid, yield 48%. mp.167–170 °C; IR (KBr, cm−1):
3442.6, 2920.4, 2851.6, 1621.6, 1491.9, 1443.3, 1384.0,
1
1327.3, 1274.9, 1224.2, 1126.5, 1021.8, 1000.2, 762.3; H-
NMR (600 MHz, CDCl3): δ 4.22(s, 2H, S-CH2), 4.60(d, 2H,
N-CH), 6.29(d, 1H, J = 6 Hz, H-19), 6.33(d, 1H, J = 6 Hz, H-
21), 7.20(dd, 1H, J = 6 Hz, 6 Hz, H-20), 7.25(s, 1H, H-10);
13C-NMR (101 MHz, DMSO-d6) δ 162.24 (C=O), 153.01 (C-
1), 142.30 (C-11), 141.61 (C-14), 136.54 (C-2), 131.76 (C-6),
127.47, 126.19, 110.91, 109.42, 108.89, 107.19 (Ar-H), 35.65
(NH-CH2), 25.88 (C-3); HRMS (ESI) m/z (neg): 393.932823,
C14H9BrN3O2S2 [M-H]-(calcd. 393.932504); purity (HPLC):
99.41%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(3,4-difluorophenyl)piper-
azine (8d): white solid, yield 44%. mp. 190–192 °C; IR
(KBr, cm−1): 3444.2, 2919.8, 1656.7, 1560.4, 1417.7,
1384.3, 1276.6, 1116.2; 1H-NMR (600 MHz, DMSO-d6): δ
3.12–3.16 (m, 4H, Ar-N(CH2)2), 3.70–3.74(t, 4H, CON
(CH2)2), 4.27(s, 2H, S-CH2), 6.72–6.77(m, 1H, Ar-H),
7.00–7.04 (m, 1H, Ar-H), 7.25 (d, 1H, J = 9.6 Hz, Ar-H),
7.45(s, 1H, H-10); 13C-NMR (101 MHz, DMSO-d6) δ
160.06 (C=O), 151.31 (C-16), 149.02 (C-1), 148.71 (C-14),
148.63 (C-17), 144.71 (C-2), 142.22 (C-6), 126.26, 117.84,
117.67, 112.02, 108.94, 105.38, 105.17 (Ar-H), 49.46,
48.86 (C-11, C-12), 46.47, 41.97 (C-10, C-13), 26.01 (C-3);
HRMS (ESI) m/z (neg): 494.976868, C19H14BrF2N4OS2
[M-H]-(calcd. 494.976595); purity (HPLC): 99.44%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(4-fluorophenyl) piperazine
(8e): white solid. mp. 185–186 °C; IR (KBr, cm−1): 3443,
2922, 2852, 1605, 1507, 1443, 1384, 1225, 1116; 1H-NMR
(600 MHz, CDCl3): δ 3.17–3.23 (m, 4H, Ar-N(CH2)2),
4.02–4.05 (m, 4H, CON(CH2)2), 4.24 (s, 2H, S-CH2),
7.0–7.04 (m, 4H, Ar-H), 7.24 (s, 1H, H-10); 13C-MR
(101 MHz, DMSO-d6) δ 162.01 (C=O), 157.93 (C-17),
148.18 (C-1), 142.34 (C-14), 135.82 (C-2), 131.87 (C-6),
127.47, 126.15, 118.22, 118.14, 115.91, 115.70, 110.66,
108.96 (Ar-H), 50.31, 49.71 (C-11, C-12), 46.72, 42.14 (C-
10, C-13), 26.09 (C-3); HRMS (ESI) m/z (neg):
476.986845, C19H15BrFN4OS2 [M-H]-(calcd. 476.986017);
purity (HPLC): 98.58%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(3-chloro-4-fluorophenyl)
piperazine (8a): white solid, yield 36%. mp. 120 °C; IR
(KBr, cm−1): 3233, 2924, 2853, 1745, 1609, 1586, 1502,
1464, 1382, 1223, 1154, 998; 1H-NMR (600 MHz, CDCl3):
δ 3.16(t, 4H, J = 6.0 Hz, Ar-N(CH2)2), 3.95(t, 4H, J =
6.0 Hz, CON(CH2)2), 4.26(s, 2H, S-CH2), 6.76–6.80(m, 1H,
H-23), 6.95(dd, 1H, J = 6.3 Hz, J = 2.4 Hz, H-27), 7.05
(dd, 1H, J = 8.7 Hz, J = 9 Hz, H-26), 7.25 (s, 1H, H-10);
13C-NMR (101 MHz, DMSO-d6) δ 162.00 (C=O), 152.65
(C-17), 150.28 (C-1), 148.72 (C-14), 131.84 (C-2), 130.09
(C-6), 126.26, 120.14, 119.96, 117.62, 117.41, 117.20,
116.50, 108.96 (Ar-H), 49.55, 48.97 (C-11, C-12), 46.52,
41.97 (C-10, C-13), 29.49 (C-3); HRMS (ESI) m/z (neg):
510.948158,
C19H14BrClFN4OS2
[M-H]-(calcd.
510.947045); purity (HPLC): 99.74%.
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(2-fluorophenyl)piperazine
(8b): white solid, yield 39%. mp. 78–80 °C; IR (KBr, cm−1):
3221, 2921, 2851, 1720, 1641, 1500, 1446, 1394, 1385,
1287, 1240, 1151, 999; 1H-NMR (600 MHz, CDCl3): δ 3.11
(t, 4H, J = 10.2 Hz, Ar-N(CH2)2), 4.02(t, 4H, J = 10.2 Hz,
CON(CH2)2), 4.24(s, 2H, S-CH2), 7.01–7.04(m, 3H, Ar-H),
7.23(s, 1H, H-10), 7.38(d, 1H, J = 7.8 Hz, Ar-H); 13C-NMR
(101 MHz, DMSO-d6) δ 161.62 (C=O), 156.68 (C-15),
140.01 (C-1), 139.92 (C-2), 126.27, 125.34, 125.31, 123.34,
123.26, 120.12, 120.09, 116.56, 116.36, 108.97 (Ar-H),
51.18, 50.73 (C-11, C-12), 46.99, 42.32 (C-10, C-13), 25.90
1-(7-Bromo-1,4-dihydrothieno[3’,2’:5,6]thiopyrano
[4,3-c]pyrazole-3-formyl)-4-(4-trimethoxyphenyl) piper-
azine (8f): white solid, yield 44%. mp. 90 °C; IR (KBr, cm−1):
2922, 1730, 1618, 1511, 1446, 1379, 1255, 1224, 1186, 1137,
1096, 1034, 992, 816; 1H-NMR (600 MHz, CDCl3)):
δ3.12–3.15(m, 4H, Ar-N(CH2)2), 3.96–4.03(m, 7H, CON
(C-3);
HRMS
(ESI)
m/z
(neg):
476.986542,