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H. Ying et al. / European Journal of Medicinal Chemistry 42 (2007) 226e234
400-C), 143.7 (s, 100-C), 144.5 (s, 5a-C), 149.8 (s, 9-C), 151.0
(s, 9b-C), 158.2 (s, 7-C).
1,2,3-thiadiazoline 10h. Yield: 53%, m.p. 103e106 ꢀC. ESI-
MS: m/z ¼ 603 [M þ 1]. IR (KBr): 2927, 1587 cmꢁ1
.
1H
NMR (DMSO-d6) d: 0.85 (t, J ¼ 7.2 Hz, 3H, OCH2CH3),
0.92 (t, J ¼ 7.2 Hz, 3H, OCH2CH3), 2.85e2.93 (m, 1H,
OCH2CH3), 3.11e3.19 (m, 1H, OCH2CH3), 3.36e3.50 (m,
2H, OCH2CH3), 6.14 (d, 1H, J ¼ 1.2 Hz, OCH2O), 6.17 (d,
1H, J ¼ 1.2 Hz, OCH2O), 7.10 (s, 1H, 30-H), 7.13 (d, 1H,
J ¼ 8.0 Hz, 6-H), 7.22 (s, 1H, 60-H), 7.37 (dd, 1H,
J ¼ 8.0 Hz, 1.6 Hz, 7-H), 7.75 (d, 1H, J ¼ 9.2 Hz, 600-H),
7.87 (d, 1H, J ¼ 1.6 Hz, 9-H), 9.19 (dd, 1H, J ¼ 9.2 Hz,
2.4 Hz, 500-H), 8.41 (d, 1H, J ¼ 2.4 Hz, 300-H).
4.1.2.4. (3aRS,4RS )6-Chloro-2-(2-chloro-4-nitrophenyl)-4-(2-
chlorophenyl)-3a,4-diethoxyl-7,9-dimethoxylchromane[4,3-d]-
D1,9b-1,2,3-thiadiazoline 10d. Yield: 45%, m.p. 222e224 ꢀC.
1
ESI-MS: m/z ¼ 639 [M þ 1]. IR (KBr): 2972, 1603 cmꢁ1. H
NMR (CDCl3) d: 0.91 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 1.01 (t,
3H, J ¼ 7.2 Hz, OCH2CH3), 2.87e2.95 (m, 1H, OCH2CH3),
3.22e3.29 (m, 1H, OCH2CH3), 3.45e3.61 (m, 2H, OCH2CH3),
4.03 (s, 3H, 3H, OCH3), 4.05 (s, 3H, OCH3), 6.39 (s, 1H, 6-H),
7.30e7.35 (m, 2H, 40-H and 50-H), 7.42e7.44 (m, 1H, 60-H),
7.71 (d, 1H, J ¼ 9.2 Hz, 500-H), 7.87e7.69 (m, 1H, 30-H), 8.10
(d, 1H, J ¼ 9.2, 600-H), 8.29 (s, 1H, 300-H).
4.1.2.9. (3aRS,4RS )4-(2-Chloro-4,5-dimethoxyphenyl)-2-(2-
chloro-4-nitrophenyl)-3a,4-diethoxyl-8-methylchromane[4,3-
d]-D1,9b-1,2,3-thiadiazoline 10i. Yield: 37%, m.p. 105e
107 ꢀC. ESI-MS: m/z ¼ 619 [M þ 1]. IR (KBr): 2977,
4.1.2.5.
(3aRS,4RS )6-Chloro-2-(2-chloro-4-nitrophenyl)-
1
4-(4-methylphenyl)-3a,4-diethoxyl-7,9-dimethoxylchromane
[4,3-d]-D1,9b-1,2,3-thiadiazoline 10e. Yield: 58%, m.p. 134e
136 ꢀC. ESI-MS: m/z ¼ 619 [M þ 1]. IR (KBr): 2927,
1582 cmꢁ1. H NMR (DMSO-d6) d: 0.81 (t, 3H, J ¼ 7.2 Hz,
OCH2CH3), 0.89 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 2.37 (s, 3H,
CH3), 2.80e2.87 (m, 1H, OCH2CH3), 3.05e3.12 (m, 1H,
OCH2CH3), 3.31e3.37 (m, 1H, OCH2CH3), 3.41e3.48 (m,
1H, OCH2CH3), 3.73 (s, 3H, OCH3), 3.78 (s, 3H, OCH3),
6.97 (s, 1H, 30-H), 7.10 (d, 1H, J ¼ 8.4, 6-H), 7.21 (s, 1H,
60-H), 7.32 (dd, 1H, J ¼ 8.0 Hz, 1.6 Hz, 7-H), 7.71 (d, 1H,
J ¼ 9.2 Hz, 600-H), 7.31 (dd, 1H, J ¼ 8.4 Hz, 1.6 Hz, 7-H),
7.83 (d, 1H, J ¼ 1.6 Hz, 9-H), 8.15 (dd, 1H, J ¼ 9.2 Hz,
2.4 Hz, 500-H), 8.28 (d, 1H, J ¼ 2.4 Hz, 300-H).
1
1598 cmꢁ1. H NMR (DMSO-d6) d: 0.82 (t, 3H, J ¼ 7.2 Hz,
OCH2CH3), 0.90 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 2.43 (s, 3H,
CH3), 2.86e2.90 (m, 1H, OCH2CH3), 3.08e3.12 (m, 1H,
OCH2CH3), 3.26e3.30 (m, 1H, OCH2CH3), 3.37e3.41 (m,
1H, OCH2CH3), 6.41 (s, 1H, 8-H), 7.03 (d, 2H, J ¼ 8.8 Hz,
30-H and 50-H), 7.22 (d, 2H, J ¼ 8.8 Hz, 20-H and 60-H), 7.75
(d, 1H, J ¼ 9.2 Hz, 600-H), 8.19 (dd, 1H, J ¼ 9.2 Hz, 2.8 Hz,
500-H), 8.39 (d, 1H, J ¼ 2.8 Hz, 300-H).
4.1.2.10. (3aRS,4RS )2-(2-Chloro-4-nitrophenyl)-3a,4-dieth-
4.1.2.6.
(3aRS,4RS )6-Chloro-2-(2-chloro-4-nitrophenyl)-
oxyl-4-(4-methoxylphenyl)-8-methylchromane[4,3-d]-D1,9b
-
4-(4-methoxylphenyl)-3a,4-diethoxyl-7,9-dimethoxylchromane[4,3-
1,2,3-thiadiazoline 10j. Yield: 53%, m.p. 221e224 ꢀC. ESI-
d]-D1,9b-1,2,3-thiadiazoline 10f. Yield: 40%, m.p. 171e173 ꢀC.
MS: m/z ¼ 555 [M þ 1]. IR (KBr): 2927, 1589 cmꢁ1
.
1H
1
ESI-MS: m/z ¼ 635 [M þ 1]. IR (KBr): 2927, 1583 cmꢁ1. H
NMR (CDCl3) d: 0.89 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 0.99
(t, 3H, J ¼ 7.2 Hz, OCH2CH3), 2.85e2.93 (m, 1H,
OCH2CH3), 3.21e3.27 (m, 1H, OCH2CH3), 3.43e3.60 (m,
2H, OCH2CH3), 3.92 (s, 3H, OCH3), 6.93 (d, 2H,
J ¼ 8.8 Hz, 30-H and 50-H), 7.18 (d, 1H, J ¼ 8.4 Hz, 6-H),
7.38 (dd, 1H, J ¼ 8.4 Hz, 1.6 Hz, 7-H), 7.61 (d, 2H,
J ¼ 8.8 Hz, 20-H and 60-H), 7.73 (d, 1H, J ¼ 9.2 Hz, 500-H),
7.89 (d, 1H, J ¼ 1.6 Hz, 9-H), 8.10 (d, 1H, J ¼ 9.2 Hz, 600-
H), 8.29 (s, 1H, 300-H).
NMR (CDCl3) d: 0.88 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 1.00 (t,
3H, J ¼ 7.2 Hz, OCH2CH3), 2.84e2.92 (m, 1H, OCH2CH3),
3.19e3.26 (m, 1H, OCH2CH3), 3.34e3.42 (m, 1H, OCH2CH3),
3.48e3.56 (m, 1H, OCH2CH3), 3.85 (s, 3H, OCH3), 3.98 (s, 3H,
OCH3), 4.02 (s, 3H, OCH3), 6.61 (s, 1H, 8-H), 6.94 (d, 2H,
J ¼ 8.8 Hz, 30-H and 50-H), 7.60 (d, 2H, J ¼ 8.8 Hz, 20-H and 60-
H), 7.69 (d, 1H, J ¼ 9.2 Hz, 600-H), 8.08 (dd, 1H, J ¼ 9.2 Hz,
1.6 Hz, 500-H), 8.30 (d, 1H, J ¼ 1.6 Hz, 300-H).
4.1.2.7. (3aRS,4RS )2-(2-Chloro-4-nitrophenyl)-4-(4-chloro-
phenyl)-3a,4-diethoxyl-8-methylchromane[4,3-d]-D1,9b-1,2,3-
thiadiazoline 10g. Yield: 76%, m.p. 172e174 ꢀC. ESI-MS: m/
4.1.2.11.
(3aRS,4RS )2-[2-Chloro-4-nitrophenyl]-4-phenyl-
3a,4,7,9-tetramethoxylchromane[4,3-d]-D1,9b-1,2,3-thiadiazo-
line 10k. Yield: 52%, m.p. 107e108 ꢀC. ESI-MS: m/z ¼ 611
1
z ¼ 559 [M þ 1]. IR (KBr): 2977, 1582 cmꢁ1
.
1H NMR
[M þ 1]. IR (KBr): 2980, 1597 cmꢁ1. H NMR (CDCl3) d:
(DMSO-d6) d: 0.80 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 0.89 (t,
3H, J ¼ 7.2 Hz, OCH2CH3), 2.38 (s, 3H, CH3), 2.86e2.90
(m, 1H, OCH2CH3), 3.07e3.11 (m, 1H, OCH2CH3), 3.24e
3.28 (m, 1H, OCH2CH3), 3.35e3.39 (m, 1H, OCH2CH3),
7.18 (d, 1H, J ¼ 8.4 Hz, 6-H), 7.38 (dd, 1H, J ¼ 8.4 Hz,
1.6 Hz, 7-H), 7.56 (d, 2H, J ¼ 8.8 Hz, 30-H and 50-H), 7.64
(d, 2H, J ¼ 8.8 Hz, 20-H and 60-H), 7.74 (d, 1H, J ¼ 9.2 Hz,
600-H), 7.89 (d, 1H, J ¼ 1.6 Hz, 9-H), 8.21 (dd, 1H,
J ¼ 9.2 Hz, 2.8 Hz, 500-H), 8.42 (d, 1H, J ¼ 2.8 Hz, 300-H).
2.90 (s, 3H, OCH3), 3.13 (s, 3H, OCH3), 4.03 (s, 3H,
OCH3), 4.06 (s, 3H, OCH3), 6.41 (s, 1H, 8-H), 7.43 (d, 2H,
J ¼ 8.4 Hz, 30-H and 50-H), 7.57e7.72 (m, 3H, 20-H, 60-H
and 600-H), 8.10 (d, 1H, J ¼ 9.6 Hz, 500-H), 8.30 (s, 1H, 300-H).
4.1.2.12. (3aRS,4RS )2-[2-Chloro-4-(methylsulfonyl)-phenyl]-
4-(4-chlorophenyl)-3a,4-diethoxylchromane[4,3-d]-D1,9b
-
1,2,3-thiadiazoline 11a. Yield: 78%, m.p. 112e113 ꢀC. ESI-
MS: m/z ¼ 578 [M þ 1]. IR (KBr): 2954, 1608 cmꢁ1
.
1H
NMR (CDCl3) d: 0.90 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 0.95
(t, 3H, J ¼ 7.2 Hz, OCH2CH3), 2.91e2.95 (m, 1H,
OCH2CH3), 3.08 (s, 3H, SO2CH3), 3.27e3.46 (m, 3H,
4.1.2.8. (3aRS,4RS )4-(6-Chlorobenzo[d][1,3]dioxol-5-yl)-2-
(4-nitrophenyl)-3a,4-diethoxyl-8-methylchromane[4,3-d]-D1,9b
-