C. Zhao et al. / Bioorg. Med. Chem. 14 (2006) 2552–2558
2557
J = 7.2 Hz, –OCH2CH3), 4.27 (s, 2H, –CH2N<), 5.09 (s,
2H, –CH2–sulfonyl–), 6.96–7.25 (m, 4H, –PhH), 7.54 (d,
2H, –UH); MS: m/z 471.1 [MH+].
NMR (CDCl3) d 0.98 (m, 2H, –N–CH(CH2)2), 1.21
(m, 2H, –N–CH(CH2)2), 1.41 (t, 3H, J = 7.2 Hz,
–OCH2CH3), 1.66 (m, 6H, –piperidinyl H), 2.68 (m,
1H, –N–CH(CH2)2), 3.43 (m, 4H, –piperidinyl H), 4.05
(d, 2H, –CH2–furanyl–), 4.38 (q, 2H, J = 6.9 Hz,
–OCH2CH3), 4.51 (d, 2H, J = 3 Hz, –CH2N<), 5.10 (s,
2H, –CH2–sulfonyl–), 6.40–6.90 (m, 3H, –furanyl H),
7.43–7.46 (d, 2H, –UH); MS: m/z 501.1 [MH+].
4.1.8.3. Ethyl 4-(pyrrolidinylmethyl)-5-hydroxy-1-
methyl-2-[(3-methoxyphenyl)sulfonylmethyl]-1H-indole-
3-carboxylate (10J). Mp: 179–181 °C; 1H NMR (DMSO-d6)
d 1.31 (t, 3H, J = 7.2 Hz, –OCH2CH3), 1.90 (m, 4H,
–pyrrolidinyl H), 3.35 (m, 4H, –pyrrolidinyl H), 3.68 (s,
3H, –NCH3), 3.70 (s, 3H, m-OCH3 of phenyl), 4.15 (q,
2H, J = 7.2 Hz, –OCH2CH3), 4.80 (s, 2H, –CH2N<), 5.39
(s, 2H, –CH2–sulfonyl–), 7.09–7.36 (m, 4H, –PhH), 7.56
(d, 2H, –UH); MS: m/z 487.0 [MH+].
4.1.9. General procedure for the synthesis of compounds
10P–T. To a solution of imidazole (0.1 mol) in anhydrous
ethanol (50 ml) was added 9 (0.02 mol) at 78 °C with
constant stirring. The solid was dissolved about 1 h lat-
er. The reaction mixture was further stirred with reflux-
ing until a mass of solid appeared in the solution. The
precipitate was filtered, dried, and gave the desired com-
pounds 10P–T (73.2%).
4.1.8.4. Ethyl 4-(pyrrolidinylmethyl)-5-hydroxy-1-
methyl-2-[(3,4-dimethoxyphenyl)sulfonylmethyl]-1H-
1
indole-3-carboxylate (10K). Mp: 184–186 °C; H NMR
(CDCl3) d 1.32 (t, 3H, J = 7.2 Hz, –OCH2CH3), 1.90
(m, 4H, –pyrrolidinyl H), 2.73 (m, 4H, –pyrrolidinyl
H), 3.75 (s, 3H, –NCH3), 3.79 (s, 3H, m-OCH3-phenyl),
3.91 (s, 3H, p-OCH3-phenyl), 4.04 (q, 2H, J = 7.2 Hz,
–OCH2CH3), 4.28 (s, 2H, –CH2N<), 5.12 (s, 2H,
–CH2–sulfonyl–), 6.94–7.28 (m, 3H, –PhH), 7.56 (d,
2H, –UH); MS: m/z 517.1 [MH+].
4.1.9.1.
Ethyl
4-(1-imidazolylmethyl)-5-hydroxy-
1-cyclopropyl-2-[(4-methylphenyl)sulfonylmethyl]-1H-
indole-3-carboxylate (10P). Mp: 197–199 °C; 1H
NMR (DMSO-d6) d 1.01 (m, 2H, –N–CH(CH2)2),
1.14 (t, 3H, J = 7.2 Hz, –OCH2CH3), 1.28 (m, 2H,
–N–CH(CH2)2), 2.39 (s, 3H, p-CH3-phenyl), 3.01
(m, 1H, –N–CH(CH2)2), 3.96 (q, 2H, J = 7.2 Hz,
–OCH2CH3), 5.27 (s, 2H, –CH2–sulfonyl), 5.69 (s,
2H, –CH2N<), 7.10–7.41 (m, 3H, –imidazolyl H),
7.44–7.61 (m, 4H, –PhH), 7.67 (d, 2H, –UH); MS:
m/z 492.0 [MH+].
4.1.8.5. Ethyl 4-(pyrrolidinylmethyl)-5-hydroxy-1-
cyclopropyl-2-[(2-furanylmethyl)sulfonylmethyl]-1H-
indole-3-carboxylate (10L). Mp: 195–197 °C; 1H NMR
(CDCl3) d 0.96 (m, 2H, –N–CH(CH2)2), 1.22 (m, 2H,
–N–CH(CH2)2), 1.37 (t, 3H, J = 7.2Hz, –OCH2CH3),
1.93 (m, 4H, –pyrrolidinyl H), 2.70 (m, 4H, –pyrrolidi-
nyl H), 2.78 (m, 1H, –N–CH(CH2)2), 4.09 (d, 2H,
–CH2–furanyl–), 4.40 (q, 2H, J = 6.9 Hz, –OCH2CH3),
4.52 (d, 2H, J = 3 Hz, –CH2N<), 5.15 (s, 2H, –CH2–sul-
fonyl–), 6.41–6.88 (m, 3H, –furanyl H), 7.41–7.45 (d,
2H, –UH); MS: m/z 487.0 [MH+].
4.1.9.2. Ethyl 4-(1-imidazolylmethyl)-5-hydroxy-1-
cyclopropyl-2-[(4-methoxyphenyl)sulfonylmethyl]-1H-
indole-3-carboxylate (10Q). Mp: 177–179 °C; H NMR
(DMSO-d6) d 1.02 (m, 2H, –N–CH(CH2)2), 1.17 (t,
3H, J = 7.2 Hz, –OCH2CH3), 1.29 (m, 2H, –N–
CH(CH2)2), 3.05 (m, 1H, –N–CH(CH2)2), 3.93 (s,
1
3H, p-OCH3-phenyl), 3.99 (q, 2H, J = 7.2 Hz,
–
4.1.8.6. Ethyl 4-(morpholinomethyl)-5-hydroxy-1-meth-
dimethoxyphenyl)sulfonylmethyl]-1H-indole-3-carboxyl-
ate (10M). Mp: 192–194 °C; 1H NMR (CDCl3)
d 1.31 (t, 3H, J = 7.2 Hz, –OCH2CH3), 2.58 (m, 4H,
–morpholino H), 3.55 (s, 3H, –NCH3), 3.73 (m, 4H,
–morpholino H), 3.75 (s, 3H, m-OCH3-phenyl), 3.93
(s, 3H, p-OCH3-phenyl), 4.03 (q, 2H, J = 7.2 Hz,
–OCH2CH3), 4.09 (s, 2H, –CH2N<), 5.07 (s, 2H,
–CH2–sulfonyl–), 6.78–6.93 (m, 3H, –PhH), 7.18–7.36
(d, 2H, –UH); MS: m/z 533.0 [MH+].
OCH2CH3), 5.28 (s, 2H, –CH2–sulfonyl), 5.66 (s, 2H,
–CH2N<), 7.15–7.43 (m, 3H, –imidazolyl H), 7.48–
7.62 (m, 4H, –PhH), 7.69 (d, 2H, –UH); MS: m/z
510.0 [MH+].
4.1.9.3. Ethyl 4-(2-methyl-1-imidazolylmethyl)-5-
hydroxy-1-cyclopropyl-2-[(4-methoxyphenyl) sulfonylm-
ethyl]-1H-indole-3-carboxylate (10R). Mp: 178–180 °C;
1H NMR (DMSO-d6) d 1.09 (m, 2H, –N–CH(CH2)2),
1.12 (t, 3H, J = 7.2 Hz, –OCH2CH3), 1.28 (m, 2H,
–N–CH(CH2)2), 2.33 (s, 3H, 2-CH3-1-imidazolyl), 2.96
(m, 1H, –N–CH(CH2)2), 3.91 (s, 3H, p-OCH3-phenyl),
4.01 (q, 2H, J = 7.2 Hz, –OCH2CH3), 5.29 (s, 2H,
–CH2N<), 5.36 (s, 2H, –CH2–sulfonyl–), 6.24–6.58 (m,
2H, –imidazolyl H), 6.93–7.66 (m, 4H, –PhH), 7.72–
7.79 (d, 2H, –UH); MS: m/z 524.0 [MH+].
4.1.8.7. Ethyl 4-(morpholinomethyl)-5-hydroxy-1-
cyclopropyl-2-[(2-furanylmethyl)sulfonylmethyl]-1H-
indole-3-carboxylate (10N). Mp: 196–198 °C; 1H NMR
(CDCl3) d 0.95 (m, 2H, –N–CH(CH2)2), 1.22 (m, 2H,
–N–CH(CH2)2), 1.38 (t, 3H, J = 7.2 Hz, –OCH2CH3),
2.59 (m, 4H, –morpholino H), 2.69 (m, 1H, –N–
CH(CH2)2), 3.71 (m, 4H, –morpholino H), 4.04 (d,
2H, –CH2–furanyl–), 4.35 (q, 2H, J = 6.9 Hz,
–OCH2CH3), 4.55 (d, 2H, J = 3Hz, –CH2N<), 5.12 (s,
2H, –CH2–sulfonyl–), 6.45–6.93 (m, 3H, –furanyl H),
7.40–7.44 (d, 2H, –UH); MS: m/z 503.0 [MH+].
4.1.9.4. Ethyl 4-(2-methyl-1-imidazolylmethyl)-5-
hydroxy-1-cyclopropyl-2-[(3,4-difluoro-phenyl)sulfonylm-
ethyl]-1H-indole-3-carboxylate (10S). Mp: 181–183 °C;
1H NMR (DMSO-d6) d 1.06 (m, 2H, –N–CH(CH2)2),
1.10 (t, 3H, J = 7.2 Hz, –OCH2CH3), 1.27 (m, 2H,
–N–CH(CH2)2), 2.30 (s, 3H, 2-CH3-1-imidazolyl), 2.98
(m, 1H, –N–CH(CH2)2), 3.95 (q, 2H, J = 7.2Hz,
–OCH2CH3), 5.30 (s, 2H, –CH2N<), 5.39 (s, 2H,
–CH2–sulfonyl–), 6.25–6.51 (m, 2H, –imidazolyl H),
4.1.8.8. Ethyl 4-(piperidinylmethyl)-5-hydroxy-1-
cyclopropyl-2-[(2-furanylmethyl)sulfonylmethyl]-1H-
indole-3-carboxylate (10O). Mp: 200–202 °C; 1H