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H.-S. Chen et al. / Bioorg. Med. Chem. 16 (2008) 1262–1278
J = 7.1 Hz), 5.70 (s, 2H), 6.98–7.04 (m, 2H), 7.09–7.14
(m, 1H), 7.19–7.24 (m, 3H), 7.27–7.34 (m,1H), 7.56 (d,
1H, J = 8.4 Hz), 7.69 (d, 3H, J = 8.3 Hz), 8.09 (d, 2H,
J = 8.3 Hz); 13C NMR (50 MHz, DMSO-d6): d 14.35,
54.39, 61.20, 117.51, 120.12, 121.19, 122.62, 126.52,
127.15 (C · 2), 127.84, 128.78 (C · 2), 129.84 (C · 2),
130.07 (C · 3), 133.75, 134.62, 137.04, 147.80, 165.48.
(C · 2), 129.08, 129.49 (C · 2), 130.04 (C · 2), 132.53,
136.43, 137.80, 141.22, 141.92, 165.74.
4.11.4. Ethyl 4-[1-(2-fluorobenzyl)-1H-indazol-3-yl]ben-
zoate (35). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 2-fluorobenzyl chloride (24)
(21.7 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 35,
yield 3.19 g, 56.9%; mp 94–96 ꢁC; MS (EI, 70 eV): m/z
374 (M+); C23H19FN2O2; UV kmax (loge): 211 (4.7),
4.11. Preparation of ethyl 4-[1-(substituted benzyl)-1H-
indazol-3-yl]benzoate (32–40)
320 (4.5); IR (KBr): 1612 (C@N), 1719 (C@O) cmꢀ1
;
4.11.1. Ethyl 4-[1-(2-chlorobenzyl)-1H-indazol-3-yl]ben-
zoate (32). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 2-chlorobenzyl chloride (21)
(24.3 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 32,
yield 3.20 g, 54.6%; mp 93–95 ꢁC; MS (EI, 70 eV): m/z
390.5 (M+); found: C, 70.70; H, 4.89; N, 7.15.
C23H19ClN2O2 requires: C, 70.68; H, 4.90; N, 7.17;
UV kmax (loge): 211 (4.7), 321 (4.6); IR (KBr): 1609
1H NMR (200 MHz, DMSO-d6): d 1.33 (t, 3H,
J = 7.1 Hz), 4.33 (q, 2H, J = 7.1 Hz), 5.80 (s, 2H),
7.11–7.32 (m, 5H), 7.44–7.52 (m, 1H), 7.80 (d, 1H,
J = 8.5 Hz), 8.05–8.16 (m, 5H); 13C NMR (50 MHz,
DMSO-d6): d 14.41, 46.27, 60.99, 110.64, 115.74,
121.16 (C · 2), 122.23, 124.17, 124.93, 126.99 (C · 3),
129.10, 130.03, 130.18 (C · 2), 130.27, 137.77, 141.34,
141.99, 160.21, 165.74.
(C@N), 1711 (C@O) cmꢀ1
;
1H NMR (200 MHz,
4.11.5. Ethyl 4-[1-(3-fluorobenzyl)-1H-indazol-3-yl]ben-
zoate (36). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 3-fluorobenzyl chloride (25)
(21.7 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 36,
yield 2.97 g, 53.0%; mp 86–87 ꢁC; MS (EI, 70 eV): m/z
374 (M+); C23H19FN2O2; UV kmax (loge): 211 (4.7),
DMSO-d6): d 1.32 (t, 3H, J = 7.1 Hz), 4.32 (q, 2H,
J = 7.1 Hz), 5.82 (s, 2H), 6.87 (dd, 1H, J = 1.7,
7.6 Hz), 7.18–7.34 (m, 3H), 7.42–7.51 (m, 2H), 7.74 (d,
1H, J = 8.5 Hz), 8.04–8.18 (m, 5H); 13C NMR
(50 MHz, DMSO-d6): d 14.41, 49.96, 60.98, 110.65,
121.16 (C · 2), 122.27, 127.00 (C · 3), 127.74, 129.11,
129.38, 129.72 (C · 2), 130.02 (C · 2), 132.23, 134.74,
137.73, 141.62, 142.16, 165.72.
320 (4.5); IR (KBr): 1611 (C@N), 1707 (C@O) cmꢀ1
;
1H NMR (200 MHz, DMSO-d6): d 1.33 (t, 3H,
J = 7.1 Hz), 4.33 (q, 2H, J = 7.1 Hz), 5.78 (s, 2H),
7.07–7.14 (m, 3H), 7.24–7.36 (m, 2H), 7.43–7.51 (m,
1H), 7.82 (d, 1H, J = 8.5 Hz), 8.06–8.18 (m, 5H); 13C
NMR (50 MHz, DMSO-d6): d 14.41, 51.64, 60.99,
110.71, 114.33, 114.76, 121.21, 121.27, 122.27, 123.64,
127.02 (C · 3), 129.11, 130.05 (C · 2), 130.93, 137.78,
140.23, 141.29, 141.99, 162.37, 165.74.
4.11.2. Ethyl 4-[1-(3-chlorobenzyl)-1H-indazol-3-yl]ben-
zoate (33). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 3-chlorobenzyl chloride (22)
(24.3 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 33,
yield 2.88 g, 49.2%; mp 76–77 ꢁC; MS (EI, 70 eV): m/z
390.5 (M+); found: C, 70.71; H, 4.89; N, 7.16.
C23H19ClN2O2 requires: C, 70.68; H, 4.90; N, 7.17;
UV kmax (loge): 211 (4.6), 320 (4.5); IR (KBr): 1609
4.11.6. Ethyl 4-[1-(4-fluorobenzyl)-1H-indazol-3-yl]ben-
zoate (37). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 4-fluorobenzyl chloride (26)
(21.7 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 37,
yield 3.13 g, 55.8%; mp 79–80 ꢁC; MS (EI, 70 eV): m/z
374 (M+); C23H19FN2O2; UV kmax (loge): 211 (4.6),
(C@N), 1713 (C@O) cmꢀ1
;
1H NMR (200 MHz,
DMSO-d6): d 1.33 (t, 3H, J = 7.0 Hz), 4.33 (q, 2H,
J = 7.0 Hz), 5.78 (s, 2H), 7.20–7.37 (m, 5H), 7.44–7.52
(m, 1H), 7.83 (d, 1H, J = 8.4 Hz), 8.06–8.17 (m, 5H);
13C NMR (50 MHz, DMSO-d6): d 14.42, 51.52, 61.01,
110.71, 121.25 (C · 2), 122.32, 126.27, 127.03 (C · 3),
127.45, 127.86, 129.12, 130.07 (C · 2), 130.83, 133.40,
137.75, 139.91, 141.28, 142.02, 165.74.
320 (4.4); IR (KBr): 1609 (C@N), 1711 (C@O) cmꢀ1
;
1H NMR (200 MHz, DMSO-d6): d 1.32 (t, 3H,
J = 7.1 Hz), 4.32 (q, 2H, J = 7.1 Hz), 5.74 (s, 2H),
7.08–7.22 (m, 2H), 7.26–7.39 (m, 3H), 7.41–7.49 (m,
1H), 7.80 (d, 1H, J = 8.5 Hz), 8.06–8.17 (m, 5H); 13C
NMR (50 MHz, DMSO-d6): d 14.39, 51.52, 60.97,
110.72, 115.63 (C · 2), 121.16, 121.30, 122.18, 126.96
(C · 3), 129.06, 129.76 (C · 2), 130.02 (C · 2), 133.62,
137.85, 141.14, 141.84, 161.83, 165.74.
4.11.3. Ethyl 4-[1-(4-chlorobenzyl)-1H-indazol-3-yl]ben-
zoate (34). Compound 17 (4.0 g, 0.015 mol), EtONa
(3.5 g, 0.052 mol), and 4-chlorobenzyl chloride (23)
(24.3 mL, 0.15 mol) were allowed to react as in the prep-
aration of compound 30 (YD-3) to afford compound 34,
yield 3.39 g, 57.9%; mp 89–91 ꢁC; MS (EI, 70 eV): m/z
390.5 (M+); found: C, 70.70; H, 4.88; N, 7.18.
C23H19ClN2O2 requires: C, 70.68; H, 4.90; N, 7.17;
UV kmax (loge): 211 (4.7), 320 (4.5); IR (KBr): 1611
4.11.7.
Ethyl
4-[1-(2-methoxybenzyl)-1H-indazol-3-
yl]benzoate (38). Compound 17 (4.0 g, 0.015 mol),
EtONa (3.5 g, 0.052 mol), and 2-methoxybenzyl chlo-
ride (27) (21 mL, 0.15 mol) were allowed to react as in
the preparation of compound 30 (YD-3) to afford com-
pound 38, yield 3.42 g, 56.9%; mp 80–81 ꢁC; MS (EI,
70 eV): m/z 386 (M+); found: C, 74.67; H, 5.72; N,
7.22. C24H22N2O3 requires: C, 74.59; H, 5.74; N, 7.25;
UV kmax (loge): 211 (4.7), 320 (4.5); IR (KBr): 1611
(C@N), 1719 (C@O) cmꢀ1
;
1H NMR (200 MHz,
DMSO-d6): d 1.33 (t, 3H, J = 7.1 Hz), 4.33 (q, 2H,
J = 7.1 Hz), 5.76 (s, 2H), 7.24–7.39 (m, 5H), 7.43–7.50
(m, 1H), 7.80 (d, 1H, J = 8.4 Hz), 8.06–8.17 (m, 5H);
13C NMR (50 MHz, DMSO-d6): d 14.42, 51.51, 61.00,
110.72, 121.20, 121.28, 122.25, 126.99 (C · 3), 128.84