J. W. Human et al. / Bioorg. Med. Chem. 8 (2000) 439±447
445
J=7.5 Hz, 2H), 8.18 (d, J=7.5 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3) d 55.5, 55.6, 92.3, 94.8, 109.2, 114.9,
119.8, 122.0, 123.4, 124.4, 125.5, 128.8, 129.1, 132.3,
136.2, 138.2, 141.1, 156.0, 160.2; MS (EI) m/z 331
(90), 226 (10), 140 (12), 105 (100). Anal. calcd for
C21H17NO3: C, 76.12; H, 5.17; N, 4.23; found: C, 76.23;
H, 5.07; N, 4.15.
(88), 320 (100), 262 (10), 240 (20). Anal. calcd for
C19H22NO2Br: C, 60.65; H, 5.89; N, 3.72; found: C
60.38; H, 5.75; N, 3.63.
(1aR,5aR)-13-hydroxy-2,5,5-trimethyl-8-benzoyl-indolo-
[3,2-b]-l,la,4,5a-tetrahydro-5H-dibenzo[h, j]pyran (22). To
solution of 0.105 g (0.31 mmol) of 9-benzoyl-2,4-di-
methoxycarbazole in 2 mL, of CH2Cl2 at 0 ꢀC was added
0.72 mL, of BBr3 (1.0 M in CH2Cl2). The mixture was
allowed to warm to ambient temperature, and stirred
for 18 h. The reaction mixture was diluted with then,
washed with water and brine, dried (MgSO4) and the
solvent removed in vacuo, to give 0.095 g (94%) of
dihydroxycarbazole 21 which was used in the sub-
9-Benzoyl-3-bromo-2,4-dimethoxycarbazole (19). The
bromination was carried out as described above for the
preparation of 11, however, the reaction was stirred at
ambient temperature for 8 h. From 0.24 g (0.72 mmol)
of carbazole 18 there was obtained, after chromato-
graphy (petroleum ether:ethyl acetate, 92:8), 0.28 g
(95%) of 19 as a colorless solid: mp 158±159 ꢀC; H
sequent step without puri®cation: H NMR (300 MHz,
1
1
NMR (300 MHz, CDCl3) d 3.75 (s, 3H), 4.06 (s, 3H),
6.84 (s, 1H), 7.12±7.33 (m, 2H), 7.35±7.38 (m, 1H), 7.54
(t, J=7.3 Hz, 2H), 7.64±7.73 (m, 3H), 8.14 (d,
J=7.5 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) d 56.5,
60.4, 96.1, 102.4, 113.8, 115.3, 121.8, 123.9, 124.1, 125.6,
129.0, 129.1, 132.6, 135.4, 138.6, 139.9, 155.9, 169.5; MS
(EI) m/z 4H (17), 409 (18), 105 (100). Anal. calcd for
C21H16NO3Br: C, 61.48; H, 3.93; N, 3.41; found: C,
61.38; H, 3.89; N, 3.46.
DMSO-d6) d 6.32 (d, J=1.8 Hz, 1H), 6.37 (d, J=1.7 Hz,
1H), 7.08±7.17 (m, 2H), 7.19±7.27 (m, 1H), 7.55±7.82
(m, 5H), 8.06 (d, J=7.4 Hz, 1H), 9.62 (s, 1H), 10.47 (s,
1H); 13C NMR (75.5 MHz, DMSO-d6) d 94.1, 98.6,
106.3, 114.7, 121.3, 123.6, 123.9, 125.9, 128.7, 129.3,
132.6, 135.6, 137.7, 141.3, 154.1, 158.1, 169.5.
A mixture of 0.14 g (0.46 mmol) of 9-benzoyl-2,4,-di-
hydroxycarbazole, 0.15 g (1.0 mmol) of trans-p-mentha-
dienol and 0.020 g of p-toluenesulfonic acid in 20 mL of
benzene was heated at re¯ux for 20 h. The solvent was
removed in vacuo and the residue was puri®ed by chro-
matography (petroleum ether:ether, 3:1) to give 0.092 g
(40%) of 22 as a yellow gum: 1H NMR (300 MHz,
CDCl3) d 1.04 (s, 3H), 1.18±1.26 (m, 1H), 1.35 (s, 3H),
1.72 (s, 3H), 1.82 (d, J=7.8 Hz, 2H), 2.00±2.05 (m, 1H),
2.83±2.85 (m, 1H), 3.06 (dd, J=8.1, 1.9 Hz, 1H), 5.46 (s,
1H), 5.59 (s, 1H), 6.67 (s, 1H), 7.15 (t, J=7.5 Hz, 1H),
7.27 (t, J=7.2 Hz, 1H), 7.36 (d, 8.1H), 7.46 (t,
J=7.2 Hz, 2H), 7.61 (t, J=7.2 Hz, 1H), 7.69 (d, J=7.2 Hz,
2H), 8.07 (d, 7.5, 1H); 13C NMR (75.5 MHz, CDCl3) d
18.3, 23.4, 27.4, 27.9, 31.5, 36.6, 45.2, 98.1, 108.1, 108.9,
115.2, 120.1, 120.8, 123.4, 124.5, 125.5, 128.8, 129.1,
132.3, 133.9, 135.6, 138.5, 139.7, 150.7, 154.4, 169.7; MS
(EI) m/z 437 (10), 354 (11), 105 (100); HRMS calcd for
C29H27NO3: 437.1994, found 437.19941.
3-Bromo-2,4-dimethoxycarbazole. A solution of 0.70 g
.
(1.7 mmol) of 19 and 0.70 g of LiOH H2O in 10 mL of
THF and 0.5 mL, of methanol was heated at re¯ux for
5 h. After cooling the reaction mixture was poured into
water and extracted with ethyl acetate. The extracts
were washed with saturated aqueous NaHCO3 and
brine, dried (MgSO4) and the solvent was removed at
reduced pressure. The residue was chromatographed
(petroleum ether:ethyl acetate, 7:3) to give 0.45 g (72%)
of bromocarbazole as colorless crystals: mp 155±157 ꢀC;
1H NMR (300 MHz, CDCl3) d 3.92 (s, 3H), 4.08 (s, 3H),
6.71 (s, 1H), 7.23±7.29 (m, 1H), 7.37 (d, J=3.9 Hz, 2H),
8.06 (s, 1H), 8.14 (d, J=8.1 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3) d 55.7, 60.3, 90.4, 98.2, 110.2, 111.1,
120.3, 121.5, 121.8, 124.9, 139.0, 140.3, 153.2, 155.7; MS
(EI) m/z 307 (100), 305 (95), 264 (25), 262 (25), 211 (35).
Anal. calcd for C14H12BrNO2: C, 54.92; H, 3.95; N,
4.57; found: C, 55.10; H, 4.04; N, 4.54.
(1aR,5aR)-13-pentoxy-2,5,5-trimethyl-8-pentyl-indolo-
[3,2-b]-1,1a,4,5a-tetrahydro-5H-dibenzo[h, j]pyran. To a
solution of 0.18 g (0.42 mmol) of 22 in 4 mL of DMSO
at ambient temperature was added 0.15 g of powdered
KOH. After stirring for 0.5 h, 0.4 mL of 1-bromo-
pentane was added and the reaction was stirred for an
additional 18 h. The reaction mixture was poured into
saturated brine and extracted with ethyl acetate. The
extracts were washed with brine, dried (MgSO4) and the
solvent removed in vacuo. The crude product was puri-
®ed by chromatography (petroleum ether:ether, 60:1)
to give 0.16 g (80%) of product as a yellow oil: 1H
NMR (300 MHz, CDCl3) d 0.88 (t, J=6.9 Hz, 3H), 0.97
(t, J=7.2 Hz, 3H), 1.34 (s, 3H), 1.39±1.59 (m, 12H),
1.75±2.00 (m, 9H), 2.19±2.31 (m, 1H), 2.87±2.89 (m,
1H), 3.38±3.45 (m, 1H), 3.94±4.01 (m, 1H), 4.09±4.15
(m, 3H), 5.45 (s, 1H), 6.62 (s, 1H), 7.17 (t, J=6.9 Hz,
1H), 7.19±7.48 (m, 2H), 8.12 (d, J=7.8 Hz, 1H); 13C
NMR (75.5 MHz, CDCl3) d 13.9, 14.0, 18.5, 22.5, 22.7,
23.5, 27.6, 28.1, 28.4, 28.5, 29.4, 30.4, 32.6, 36.9, 43.2,
45.1, 72.7, 76.8, 92.6, 107.8, 110.5, 111.1, 118.8, 119.0,
3-Bromo-2,4-dimethoxy-9-pentylearbazole (20). To
a
solution of 0.45 g (1.46 mmol) of bromocarbazole in
9 mL of DMSO was added 0.74 g of LiOH.H2O; the
mixture was stirred at 65 ꢀC for 0.5 h and 0.19 mL of
1-bromopentane was added dropwise. The reaction mix-
ture was stirred at 65 ꢀC for 18 h, poured into 5% aqu-
eous HCl and extracted with ethyl acetate. The extracts
were washed with saturated brine, dried (MgSO4) and
the solvent was removed in vacuo. Chromatography
(petroleum ether:ethyl acetate, 93:7) provided 0.50 g
(95%) of 20 as colorless crystals: mp 159±160 ꢀC; H
1
NMR (300 MHz, CDCl3) d 0.87 (t, J=7.9 Hz, 3H),
1.25±1.43 (m, 4H), 1.82 (t, J=6.9 Hz, 2H), 3.98 (s, 3H),
4.07 (s, 3H), 4.20 (t, J=7.4 Hz, 2H), 6.64 (s, 1H), 7.23 (t,
J=7.4 Hz, 1H), 7.33 (d, J=7.5 Hz, 1H), 7.40 (t,
J=7.3 Hz, 1H), 8.17 (d, J=7.5 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3) d 13.9, 22.4, 28.4, 29.3, 43.1, 56.7,
60.2, 86.5, 97.5, 108.4, 110.6, 119.6, 120.9, 121.8, 124.6,
139.9, 141.2, 153.2, 155.5; MS (EI) m/z 377 (85), 375