W. Gu, S. Wang / European Journal of Medicinal Chemistry 45 (2010) 4692e4696
4695
saturated NaHCO3 solution, water and brine, dried over anhydrous
Na2SO4 and concentrated in vacuo. The residue was chromato-
graphed on a silica gel column (petroleum ethereacetone 100:1, v/
v) to give compound 3 as yellow oil (5.36 g, 64% yield). 1H NMR
3H, H-14), 1.32 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.33 (d, 3H, J ¼ 7 Hz,
H-17 or H-18), 1.70 (m, 1H), 1.77 (s, 3H, H-15), 1.84e2.02 (m, 4H),
2.33 (m,1H), 2.97 (m,1H, H-16), 3.69 (s, 3H, COOCH3), 3.86 (s,1H, H-
13c), 6.89 (dt, 1H, J ¼ 9.0, 2.0 Hz, H-11), 7.02 (dd, 1H, J ¼ 10.5, 2 Hz,
H-13), 7.18 (dd, 1H, J ¼ 8.0, 1.5 Hz), 7.26 (d, 1H, J ¼ 1.5 Hz), 7.30 (d,
1H, J ¼ 8.0 Hz), 7.32 (dd, 1H, J ¼ 8.5, 5.0 Hz, H-10), 8.41 (brs, 1H,
NeH). MS (ESI) m/z 420 ([M þ H]þ). Anal. Calcd for C27H30FNO2: C,
77.30; H, 7.21; N, 3.34; found C, 77.47; H, 7.32; N, 3.12.
(CDCl3, 300 MHz):
d
1.25 (d, J ¼ 7.0 Hz, 6H, 13-CH(CH3)2), 1.26 (s, 3H,
H-17), 1.35 (s, 3H, H-16), 1.60e1.84 (m, 5H), 2.27e2.40 (m, 2H), 2.76
(m, 2H), 2.91 (m, 1H), 3.65 (s, 3H, COOCH3), 7.29 (d, J ¼ 8.1 Hz, 1H,
H-11), 7.40 (dd, J ¼ 8.1, 2.1 Hz, 1H, H-12), 7.87 (d, J ¼ 2.0 Hz, 1H,
H-14). MS (ESI) m/z 329 ([M þ H]þ). Anal. Calcd for C21H28O3: C,
76.79; H, 8.59; found C, 76.58; H, 8.75.
6.2.4.5. 10-Fluoro-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6e). Yellow
6.2.4. General procedures for the syntheses of 1H-dibenzo[a,c]
carbazole derivatives (6ae6m)
powder; yield 49%; mp 140e142 ꢀC; IR (KBr, , cmꢁ1): 3398, 2958,
n
2931, 2868,1719,1570,1463, 1241, 1180. 1H NMR (CDCl3): 1.11 (s, 3H,
H-14), 1.34 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.35 (d, 3H, J ¼ 7 Hz, H-17
or H-18), 1.69 (m, 1H), 1.79 (s, 3H, H-15), 1.82e2.00 (m, 4H), 2.33 (m,
1H), 2.93 (m, 1H, H-16), 3.68 (s, 3H, COOCH3), 3.88 (s, 1H, H-13c),
6.98 (dt, 1H, J ¼ 8.5, 5.2 Hz, H-12), 7.12 (t, 1H, J ¼ 8.6 Hz), 7.18 (dd,
1H, J ¼ 8.0, 1.5 Hz), 7.26e7.34 (m, 3H), 8.48 (brs, 1H, NeH). MS (ESI)
m/z 420 ([M þ H]þ). Anal. Calcd for C27H30FNO2: C, 77.30; H, 7.21; N,
3.34; found C, 77.56; H, 7.55; N, 3.03.
To a solution of compound 3 (1.8 g, 5.5 mmol) in 20 ml of EtOH
was added 12 mmol of substituted phenylhydrazine hydrochloride
(5) and 2 ml of concentrated HCl. The mixture was refluxed for 3 h.
After cooling, the mixture was poured onto 100 ml of ice-cold water
and extracted with CH2Cl2 (3 ꢂ 80 ml). The organic layer was
combined, washed with saturated NaHCO3 solution and brine,
dried over anhydrous Na2SO4 and concentrated to give a crude
product, which was subject to a silica gel column chromatography
(petroleum ethereacetone 50:1, v/v) to afford compound 6.
6.2.4.6. 12-Chloro-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6f). Brown
6.2.4.1. 2,3,4,4a,9,13c-Hexahydro-7-isopropyl-1,4a-dimethyl-1H-dibenzo
powder; yield 57%; mp 110e112 ꢀC; IR (KBr, , cmꢁ1): 3360, 2957,
n
[a,c]carbazole-1-carboxylic acid methyl ester (6a). White powder; yield
2930, 2868, 1699, 1561, 1472, 1245, 964, 796. 1H NMR (CDCl3): 1.11
(s, 3H, H-14), 1.31 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.32 (d, 3H,
J ¼ 7 Hz, H-17 or H-18), 1.68 (m, 1H), 1.79 (s, 3H, H-15), 1.77e2.05
(m, 4H), 2.32 (m, 1H), 2.95 (m, 1H, H-16), 3.70 (s, 3H, COOCH3), 3.83
(s, 1H, H-13c), 7.05 (d, 1H, J ¼ 8 Hz), 7.15 (d, 1H, J ¼ 8 Hz), 7.23e7.30
(m, 3H), 7.40 (s, 1H), 8.42 (brs, 1H, NeH). MS (ESI) m/z 436
([M þ H]þ). Anal. Calcd for C27H30ClNO2: C, 74.38; H, 6.94; N, 3.21;
found C, 74.22; H, 6.99; N, 3.09.
61%; mp 170e172 ꢀC; IR (KBr, , cmꢁ1): 3370, 2958, 2930, 2868,
n
1700, 1460, 1441, 1263. 1H NMR (CDCl3): 1.10 (s, 3H, H-14), 1.31 (d,
3H, J ¼ 7 Hz, H-17 or H-18), 1.32 (d, 3H, J ¼ 7 Hz, H-18 or H-17), 1.69
(m, 1H), 1.77 (s, 3H, H-15), 1.80e2.00 (m, 4H), 2.30 (m, 1H), 2.91 (m,
1H, H-16), 3.68 (s, 3H, COOCH3), 3.84 (s, 1H, H-13c), 7.06e7.20 (m,
3H), 7.25 (d, 1H, J ¼ 1.5 Hz), 7.28 (d, 1H, J ¼ 8.0 Hz), 7.32 (d, 1H,
J ¼ 8.0 Hz), 7.52 (d, 1H, J ¼ 7.5 Hz), 8.35 (brs, 1H, NeH). MS (ESI) m/z
402 ([M þ H]þ), 424 ([M þ Na]þ). Anal. Calcd for C27H31NO2: C,
80.76; H, 7.78; N, 3.49; found C, 80.56; H, 7.92; N, 3.58.
6.2.4.7. 10-Chloro-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6g). Yellow
6.2.4.2. 2,3,4,4a,9,13c-Hexahydro-7-isopropyl-1,4a,12-trimethyl-1H-
powder; yield 48%; mp 76e78 ꢀC; IR (KBr, , cmꢁ1): 3367, 2956,
n
dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6b). White
2932, 2867, 1696, 1558, 1465, 1242, 736. 1H NMR (CDCl3): 1.11 (s, 3H,
H-14), 1.32 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.33 (d, 3H, J ¼ 7 Hz, H-17
or H-18), 1.69 (m, 1H), 1.80 (s, 3H, H-15), 1.80e2.05 (m, 4H), 2.33 (m,
1H), 2.98 (m, 1H, H-16), 3.68 (s, 3H, COOCH3), 3.85 (s, 1H, H-13c),
7.06e7.10 (m, 2H), 7.15 (d, 1H, J ¼ 8 Hz), 7.24 (d, 1H, J ¼ 7.5 Hz),
7.28e7.36 (m, 2H), 8.35 (brs,1H, NeH). MS (ESI) m/z 436 ([M þ H]þ).
Anal. Calcd for C27H30ClNO2: C, 74.38; H, 6.94; N, 3.21; found C,
74.51; H, 7.06; N, 3.05.
powder; yield 70%; mp 175e177 ꢀC; IR (KBr, , cmꢁ1): 3366, 2956,
n
2929, 2852,1698,1450,1382,1248, 793. 1H NMR (CDCl3): 1.11 (s, 3H,
H-14), 1.30 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.31 (d, 3H, J ¼ 7 Hz, H-18
or H-17), 1.68 (m, 1H), 1.78 (s, 3H, H-15), 1.80e2.00 (m, 4H), 2.30 (m,
1H), 2.42 (s, 3H, Ar-CH3), 2.94 (m, 1H, H-16), 3.64 (s, 3H, COOCH3),
3.85 (s, 1H, H-13c), 6.96 (d, 1H, J ¼ 8 Hz), 7.12 (s, 1H), 7.13 (dd, 1H,
J ¼ 8, 1.5 Hz), 7.24 (d, 1H, J ¼ 1.5 Hz), 7.26 (d, 1H, J ¼ 8 Hz), 7.29
(d, 1H, J ¼ 8 Hz), 8.31 (brs, 1H, NeH). MS (ESI) m/z 416 ([M þ H]þ).
Anal. Calcd for C28H33NO2: C, 80.93; H, 8.00; N, 3.37; found C, 81.08;
H, 7.89; N, 3.47.
6.2.4.8. 12-Bromo-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6h). Brown
powder; yield 58%; mp 120e122 ꢀC; IR (KBr, , cmꢁ1): 3357, 2956,
n
6.2.4.3. 2,3,4,4a,9,13c-Hexahydro-7-isopropyl-1,4a,10-trimethyl-1H-
2930, 2868, 1698, 1508, 1470, 1245, 960, 794. 1H NMR (CDCl3): 1.10
(s, 3H, H-14), 1.32 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.33 (d, 3H,
J ¼ 7 Hz, H-17 or H-18), 1.70 (m, 1H), 1.78 (s, 3H, H-15), 1.80e2.00
(m, 4H), 2.33 (m, 1H), 2.95 (m, 1H, H-16), 3.74 (s, 3H, COOCH3), 3.84
(s,1H, H-13c), 7.18 (d,1H, J ¼ 8.5 Hz), 7.21 (d,1H, J ¼ 8 Hz), 7.25e7.30
(m, 3H), 7.46 (s, 1H, H-13), 8.48 (brs, 1H, NeH). MS (ESI) m/z 480,
482 ([M þ H]þ). Anal. Calcd for C27H30BrNO2: C, 67.50; H, 6.29; N,
2.92; found C, 67.38; H, 6.21; N, 2.98.
dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6c). White
powder; yield 56%; mp 147e149 ꢀC; IR (KBr, , cmꢁ1): 3384, 2957,
n
2929, 2868, 1702, 1457, 1259, 1128, 826, 746. 1H NMR (CDCl3): 1.10
(s, 3H, H-14), 1.35 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.36 (d, 3H,
J ¼ 7 Hz, H-18 or H-17), 1.70 (m, 1H), 1.79 (s, 3H, H-15), 1.82e2.02
(m, 4H), 2.33 (m, 1H), 2.60 (s, 3H, Ar-CH3), 3.00 (m, 1H, H-16), 3.62
(s, 3H, COOCH3), 3.89 (s,1H, H-13c), 6.97 (d,1H, J ¼ 7 Hz), 7.00 (t,1H,
J ¼ 7 Hz), 7.17 (d, 1H, J ¼ 8 Hz), 7.22 (d, 1H, J ¼ 7.5 Hz), 7.28 (s, 1H),
7.30 (d, 1H, J ¼ 8 Hz), 8.24 (brs, 1H, NeH). MS (ESI) m/z 416
([M þ H]þ). Anal. Calcd for C28H33NO2: C, 80.93; H, 8.00; N, 3.37;
found C, 80.82; H, 8.11; N, 3.58.
6.2.4.9. 10-Bromo-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6i). Brown
powder; yield 40%; mp 107e110 ꢀC; IR (KBr, , cmꢁ1): 3365, 2953,
n
2932, 2866, 1702, 1523, 1467, 1242, 742. 1H NMR (CDCl3): 1.11 (s, 3H,
H-14), 1.32 (d, 3H, J ¼ 7 Hz, H-17 or H-18), 1.33 (d, 3H, J ¼ 7 Hz, H-17
or H-18), 1.69 (m, 1H), 1.80 (s, 3H, H-15), 1.80e2.00 (m, 4H), 2.35 (m,
1H), 2.97 (m, 1H, H-16), 3.69 (s, 3H, COOCH3), 3.87 (s, 1H, H-13c),
6.97 (t, 1H, J ¼ 8.0 Hz), 7.16 (d, 1H, J ¼ 8.5 Hz), 7.26e7.33 (m, 2H),
6.2.4.4. 12-Fluoro-2,3,4,4a,9,13c-hexahydro-7-isopropyl-1,4a-dimethyl-
1H-dibenzo[a,c]carbazole-1-carboxylic acid methyl ester (6d). Brown
powder; yield 58%; mp 178e180 ꢀC; IR (KBr, , cmꢁ1): 3390, 2957,
n
2933, 2869, 1714, 1574, 1453, 1245, 1182. 1H NMR (CDCl3): 1.11 (s,