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orless crystals. Mp 203ꢁ204 °C. FAB-MS m/z 439 [MH]+. 1H NMR
(200 MHz, CDCl3) d: 1.44 (9H, s), 2.49 (3H, s), 3.50–3.65 (2H, m),
3.68–3.80 (2H, m), 5.22 (1H, br s), 6.95 (1H, br s), 7.17 (1H, d,
J = 15.7 Hz), 7.34 (2H, d, J = 8.4 Hz), 7.50–7.62 (4H, m), 7.71 (1H,
d, J = 8.8 Hz), 7.92 (1H, d, J = 15.7 Hz). Anal. Calcd for
C24H27ClN4O2ꢀ0.3H2O: C, 64.87; H, 6.26; N, 12.61. Found: C,
64.96; H, 6.10; N, 12.62.
temperature for 15 h. The precipitate that formed was collected by
filtration, washed with EtOAc and dried under reduced pressure to
give 7c (50 mg, 82.0%) as a pale yellow powder. Mp 323–325 °C.
FAB-MS m/z 395 [MH]+. 1H NMR (300 MHz, DMSO-d6) d: 1.31–
1.48 (4H, m), 1.48–1.62 (2H, m), 1.62–1.80 (2H, m), 2.50 (3H, s),
2.62–2.80 (2H, m), 3.78–3.85 (2H, m), 7.37 (1H, d, J = 15.8 Hz),
7.59 (2H, d, J = 8.5 Hz), 7.77–7.87 (4H, m), 7.78 (2H, d, J = 8.5 Hz),
8.13 (2H, br s), 8.22 (1H, d, J = 15.8 Hz), 8.46 (1H, s), 10.1 (1H, br
s). Anal. Calcd for C23H27ClN4ꢀ2HClꢀ2.6H2O: C, 53.67; H, 6.70; N,
10.89. Found: C, 53.36; H, 6.32; N, 10.87.
6.1.32. tert-Butyl (1RS,2RS)-[2-({2-[(E)-2-(4-chlorophenyl)-
ethenyl]-6-methylquinazolin-4-yl}amino)cyclohexyl]-
carbamate (6j)
Compound 6j was prepared from 5c and tert-butyl (trans-2-
aminocyclohexyl)carbamate in a manner similar to that described
for 6c. Yield 73.4%, colorless crystals. Mp 248ꢁ250 °C. FAB-MS m/z
493 [MH]+. 1H NMR (200 MHz, CDCl3) d: 1.01–1.65 (4H, m), 1.34
(9H, s), 1.61–2.00 (2H, m), 2.00–2.24 (1H, m), 2.47 (3H, s), 2.58–
2.61 (1H, m), 3.58–3.81 (1H, m), 3.95–4.15 (1H, m), 4.81 (1H, d,
J = 8.4 Hz), 7.04 (1H, d, J = 6.2 Hz), 7.17 (1H, d, J = 15.8 Hz), 7.32
(2H, d, J = 8.4 Hz), 7.47–7.63 (2H, m), 7.55 (2H, d, J = 8.4 Hz), 7.68
(1H, d, J = 8.4 Hz), 7.87 (1H, d, J = 15.8 Hz). Anal. Calcd for
C28H33ClN4O2ꢀ0.2H2O: C, 67.72; H, 6.78; N, 11.28. Found: C,
67.72; H, 6.67; N, 11.10.
6.1.37. N-{2-[(E)-2-(4-Chlorophenyl)ethenyl]quinazolin-4-yl}
hexane-1,6-diamine dihydrochloride (7a)
Compound 7a was prepared from 6a in a manner similar to that
described for 7c. Yield 80.5%, colorless powder. Mp 322–323 °C.
FAB-MS m/z 381 [MH]+. 1H NMR (200 MHz, DMSO-d6) d: 1.20–
1.85 (8H, m), 2.60–2.90 (2H, m), 3.68–3.90 (2H, m), 7.40 (1H, d,
J = 15.8 Hz), 7.60 (2H, d, J = 8.5 Hz), 7.64–7.78 (1H, m), 7.75–7.85
(1H, m), 7.80 (2H, d, J = 8.5 Hz), 7.88–8.18 (5H, m), 8.25 (1H, d,
15.8 Hz), 8.67 (1H, d, J = 8.0 Hz), 10.3 (1H, br s). Anal. Calcd for
C22H25ClN4ꢀ2HClꢀ1.5H2O: C, 54.95; H, 6.29; N, 11.65. Found: C,
55.03; H, 5.99; N, 11.55.
6.1.33. tert-Butyl (1RS,2SR)-[2-({2-[(E)-2-(4-chlorophenyl)-
ethenyl]-6-methylquinazolin-4-yl}amino)cyclohexyl]carba-
mate (6k)
6.1.38. N-{2-[(E)-2-(4-Chlorophenyl)ethenyl]-5-methyl-
quinazolin-4-yl}hexane-1,6-diamine dihydrochloride (7b)
Compound 7b was prepared from 6b in a manner similar to that
described for 7c. Yield 84.2%, colorless powder. Mp 202–203 °C.
FAB-MS m/z 395 [MH]+. 1H NMR (300 MHz, DMSO-d6) d: 1.27–
1.48 (4H, m), 1.48–1.65 (2H, m), 1.65–1.80 (2H, m), 2.64–2.79
(2H, m), 2.86 (3H, s), 3.76–3.88 (2H, m), 7.33 (1H, d, J = 15.8 Hz),
7.47 (1H, d, J = 7.3 Hz), 7.57 (2H, d, J = 8.4 Hz), 7.74–7.92 (6H, m),
7.75 (2H, d, J = 8.4 Hz), 8.18 (1H, d, J = 15.8 Hz), 8.59 (1H, br s).
Anal. Calcd for C23H27ClN4ꢀ2HClꢀ2.9H2O: C, 53.11; H, 6.74; N,
10.77. Found: C, 53.36; H, 6.41; N, 10.70.
Compound 6k was prepared from 5c and tert-butyl (cis-2-amino-
cyclohexyl)carbamate in a manner similar to that described for 6c.
Yield 88.1%, pale yellow crystals. Mp 221–223 °C. FAB-MS m/z 493
[MH]+. 1H NMR (200 MHz, CDCl3) d: 1.30–2.18 (7H, m), 1.51 (9H,
s), 2.29–2.52 (1H, m), 2.49 (3H, s), 4.07–4.14 (1H, m), 4.32–4.50
(1H, m), 5.23 (1H, br s), 7.17 (1H, d, J = 15.8 Hz), 7.33 (1H, br s),
7.35 (2H, d, J = 8.4 Hz), 7.49–7.61 (4H, m), 7.70 (1H, d, J = 8.4 Hz),
7.88 (1H, d, J = 15.8 Hz). Anal. Calcd for C28H33ClN4O2ꢀ 0.2H2O: C,
67.72; H, 6.78; N, 11.28. Found: C, 67.74; H, 6.60; N, 11.27.
6.1.39. N-{2-[(E)-2-(4-Chlorophenyl)ethenyl]-7-methyl-
quinazolin-4-yl}hexane-1,6-diamine dihydrochloride (7d)
Compound 7d was prepared from 6d in a manner similar to that
described for 7c. Yield 75.8%, pale brown powder. Mp 320–323 °C.
FAB-MS m/z 395 [MH]+. 1H NMR (300 MHz, DMSO-d6) d: 1.50–1.68
(4H, m), 1.68–1.82 (2H, m), 1.82–2.00 (2H, m), 2.50 (3H, s), 2.88–
3.01 (2H, m), 4.03 (2H, dd, J = 6.5, 12.5 Hz), 7.62 (1H, d,
J = 15.8 Hz), 7.77 (1H, d, J = 8.6 Hz), 7.81 (2H, d, J = 8.5 Hz), 7.93
(1H, s), 8.00 (2H, d, J = 8.5 Hz), 8.19 (3H, br s), 8.45 (1H, d,
J = 15.8 Hz), 8.74 (1H, d, J = 8.6 Hz), 10.4 (1H, br s), 15.2 (1H, br
s). Anal. Calcd for C23H27ClN4ꢀ2HClꢀ1.5H2O: C, 55.82; H, 6.52; N,
11.32. Found: C, 56.09; H, 6.59; N, 11.13.
6.1.34. tert-Butyl cis-[4-({2-[(E)-2-(4-chlorophenyl)ethenyl]-6-
methylquinazolin-4-yl}amino)cyclohexyl]carbamate (6l)
Compound 6l was prepared from 5c and tert-butyl (cis-4-amin-
ocyclohexyl)carbamate in a manner similar to that described for
6c. Yield 80.6%, pale yellow crystals. Mp 201–202 °C. FAB-MS m/z
493 [MH]+. 1H NMR (300 MHz, CDCl3) d: 1.38 (9H, s), 1.54–1.93
(8H, m), 2.43 (3H, s), 3.60–3.74 (1H, m), 4.35–4.60 (2H, m), 5.44
(1H, d, J = 6.9 Hz), 7.08 (1H, d, J = 15.8 Hz), 7.26 (2H, d, J = 8.5 Hz),
7.31 (1H, s), 7.44–7.52 (1H, m), 7.46 (2H, d, J = 8.5 Hz), 7.64 (1H,
d, J = 8.5 Hz), 7.79 (1H, d, J = 15.8 Hz). Anal. Calcd for C28H33ClN4O2:
C, 68.21; H, 6.75; N, 11.36. Found: C, 67.91; H, 6.56; N, 11.17.
6.1.35. tert-Butyl trans-[4-({2-[(E)-2-(4-chlorophenyl)ethenyl]-
6-methylquinazolin-4-yl}amino)cyclohexyl]carbamate (6m)
Compound 6m was prepared from 5c and tert-butyl (trans-4-
aminocyclohexyl)carbamate in a manner similar to that described
for 6c. Yield 61.6%, pale brown crystals. Mp 242ꢁ243 °C. FAB-MS
m/z 493 [MH]+. 1H NMR (200 MHz, CDCl3) d: 1.22–1.60 (4H, m),
1.47 (9H, s), 2.05–2.45 (4H, m), 2.50 (3H, s), 3.40–3.75 (1H, m),
4.20–4.58 (2H, m), 5.45 (1H, d, J = 7.0 Hz), 7.17 (1H, d,
J = 16.0 Hz), 7.35 (2H, d, J = 8.4 Hz), 7.43 (1H, s), 7.48–7.60 (1H,
m), 7.54 (2H, d, J = 8.4 Hz), 7.72 (1H, d, J = 8.4 Hz), 7.68 (1H, d,
J = 16.0 Hz). Anal. Calcd for C28H33ClN4O2ꢀ0.5H2O: C, 66.99; H,
6.83; N, 11.16. Found: C, 67.29; H, 6.83; N, 10.95.
6.1.40. N-{2-[(E)-2-(4-Chlorophenyl)ethenyl]-8-methyl-
quinazolin-4-yl}hexane-1,6-diamine dihydrochloride (7e)
Compound 7e was prepared from 6e in a manner similar to that
described for 7c. Yield 96.2%, colorless powder. Mp 317–318 °C.
FAB-MS m/z 395 [MH]+. 1H NMR (300 MHz, DMSO-d6) d: 1.36–
1.48 (4H, m), 1.48–1.65 (2H, m), 1.65–1.82 (2H, m), 2.70 (3H, s),
2.68–2.92 (2H, m), 3.86 (2H, dd, J = 12.0, 6.0 Hz), 7.45–7.58 (3H,
m), 7.62–7.89 (3H, m), 7.95–8.30 (4H, m), 8.04 (1H, d,
J = 15.7 Hz), 8.19 (1H, d, J = 15.7 Hz), 8.51 (1H, d, J = 8.2 Hz), 10.4
(1H, br s). Anal. Calcd for C23H27ClN4ꢀ2HClꢀ1.5H2O: C, 55.82; H,
6.52; N, 11.32. Found: C, 55.55; H, 6.42; N, 11.08.
6.1.41. N-{6-tert-Butyl-2-[(E)-2-(4-chlorophenyl)ethenyl]-
quinazolin-4-yl}hexane-1,6-diamine dihydrochloride (7f)
Compound 7f was prepared from 6f in a manner similar to that
described for 7c. Yield 99.0%, colorless powder. Mp 195–197 °C.
FAB-MS m/z 437 [MH]+. 1H NMR (200 MHz, DMSO-d6) d: 1.31–
1.88 (8H, m), 1.39 (9H, s), 2.66–2.88 (2H, m), 3.75–3.94 (2H, m),
6.1.36. General procedure for the synthesis of 7a–m: N-{2-[(E)-
2-(4-chlorophenyl)ethenyl]-6-methylquinazolin-4-yl}hexane-
1,6-diamine dihydrochloride (7c)
To a solution of 6c (65 mg, 0.131 mmol) in EtOAc (2 mL) was
added 4 N HCl in EtOAc (5 mL) and the mixture was stirred at room