798
A. Kamal et al. / Bioorg. Med. Chem. 20 (2012) 789–800
5.25. 2-[1-(3-[(11aS)-7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-
1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl]oxybutyl)-1,2-
dihydrobenzo[c,d]indol-2-yliden]malononitrile (11f)
5.28. 2–3-[(7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-
benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy]propyl-1,2-
dihydro-1k6-naphtho[1,8-cd]isothiazole-1,1-dione (11i)
The compound 11f was prepared according to the method de-
scribed for the compound 11a, employing the compound 10f
(641 mg, 1.0 mmol). The crude product was purified by column
chromatography (MeOH/CHCl3, 2%) to afford the compound 11f
The compound 11i was prepared according to the method
described for the compound 11a, employing the compound 10i
(615 mg, 1.0 mmol). The crude product was purified by column
chromatography (MeOH/CHCl3, 2%) to afford the compound 11i
as a white solid (346 mg, 67% yield). Mp 92–96 °C; ½a D27
ꢃ
+58.4
as a white solid (353 mg, 72% yield). Mp 74–79 °C; ½a D27
ꢃ
+66.0
(c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz):
d
8.04 (d, 1H,
(c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz):
d 8.05 (d, 1H,
J = 6.7 Hz), 7.96 (d, 1H, J = 8.1 Hz), 7.70 (t, 1H, J = 5.8 Hz), 7.58 (d,
1H, J = 4.1 Hz), 7.49–7.36 (m, 3H), 6.94 (d, 1H, J = 6.5 Hz), 6.73 (s,
1H), 4.18–4.06 (m, 2H), 4.04 (t, 2H, J = 6.0 Hz), 3.94 (s, 3H), 3.86–
3.74 (m, 1H), 3.71–3.66 (m, 1H), 3.63–3.49 (m, 1H), 2.35–2.25
(m, 2H), 2.09–1.90 (m, 4H), 1.64–1.45 (m, 2H); 13C NMR (CDCl3,
150 MHz): d 162.39, 146.82, 140.46, 130.75, 129.12, 128.73,
128.48, 128.41, 126.62, 125.13, 124.46, 124.12, 120.24, 120.11,
115.51, 111.46, 110.43, 105.26, 105.06, 68.25, 67.29, 55.92, 53.59,
46.57, 38.74, 29.52, 26.18, 25.30, 24.83; ESIMS: m/z 517 (M+).
J = 7.5 Hz), 7.95 (d, 1H, J = 6.7 Hz), 7.74 (t, 1H, J = 7.5 Hz), 7.63
(d, 1H, J = 3.7 Hz), 7.55 (s, 1H), 7.46–7.38 (m, 2H), 6.87 (dd,
1H, J = 6.7 Hz), 6.80 (s, 1H), 4.31–4.12 (m, 4H), 4.00 (s, 3H),
3.87–3.78 (m, 1H), 3.74–3.67 (m, 1H), 3.62–3.53 (m, 1H),
2.51–2.42 (m, 2H), 2.34–2.26 (m, 2H), 2.09–2.00 (m, 2H); 13C
NMR (CDCl3, 150 MHz):
d 162.78, 150.84, 148.22, 141.07,
137.13, 131.53, 131.03, 130.75, 129.85, 128.35, 120.90,
120.06, 119.68, 118.55, 112.05, 111.29, 103.67, 65.86,
56.55, 54.08, 47.06, 39.12, 29.98, 28.55, 24.55; ESIMS: m/z 492
(M++1).
5.26. 2-[1-(3-[(11aS)-7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-
1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl]oxypentyl)-1,2-
dihydrobenzo[c,d]indol-2-yliden]malononitrile (11g)
5.29. 2–3-[(7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-
benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy]butyl-1,2-
dihydro-1k6-naphtho[1,8-cd]isothiazole-1,1-dione (11j)
The compound 11g was prepared according to the method de-
scribed for the compound 11a, employing the compound 10g
(655 mg, 1.0 mmol). The crude product was purified by column
chromatography (MeOH/CHCl3, 2%) to afford the compound 11g
The compound 11j was prepared according to the method de-
scribed for the compound 11a, employing the compound 10j
(629 mg, 1.0 mmol). The crude product was purified by column
chromatography (MeOH/CHCl3, 2%) to afford the compound 11j
as a white solid (302 mg, 57% yield). Mp 87–92 °C; ½a D27
ꢃ
+56.1
8.01 (d, 1H,
(c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz):
d
as a white solid (339 mg, 67% yield). Mp 75–80 °C; ½a D27
ꢃ
+38.1
J = 6.8 Hz), 7.96 (d, 1H, J = 7.5 Hz), 7.67 (t, 1H, J = 6.7 Hz), 7.58 (d,
1H, J = 3.8 Hz), 7.48–7.40 (m, 3H), 6.88 (d, 1H, J = 6.8 Hz), 6.70 (s,
1H), 4.10–3.96 (m, 2H), 3.94 (t, 2H, J = 6.7 Hz), 3.89 (s, 3H), 3.82–
3.74 (m, 1H), 3.70–3.65 (m, 1H), 3.59–3.52 (m, 1H), 2.33–2.28
(m, 2H), 2.08–1.99 (m, 2H), 1.96–1.83 (m, 4H), 1.66–1.58 (m,
(c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz):
d 8.03 (d, 1H,
J = 7.3 Hz), 7.93 (d, 1H, J = 6.7 Hz), 7.72 (t, 1H, J = 7.6 Hz), 7.64 (d,
1H, J = 3.9 Hz), 7.57(s, 1H), 7.45–7.37 (m, 2H), 6.86 (dd, 1H,
J = 6.7 Hz), 6.81 (s, 1H), 4.32–4.14 (m, 4H), 4.02 (s, 3H), 3.86–3.79
(m, 1H), 3.76–3.67 (m, 1H), 3.62–3.53 (m, 1H), 2.52–2.44 (m,
2H), 2.34–2.26 (m, 2H), 2.09–2.02 (m, 4H); 13C NMR (CDCl3,
2H); 13C NMR (CDCl3, 150 MHz):
d 162.32, 150.75, 147.69,
146.79, 140.53, 139.79, 130.68, 129.14, 128.57, 128.38, 126.62,
125.16, 124.12, 120.17, 120.05, 115.78, 111.48, 110.41, 104.91,
68.62, 68.06, 56.12, 53.59, 46.62, 40.11, 29.56, 28.61, 24.22,
23.41; ESIMS: m/z 532 (M++1).
150 MHz): d 162.38, 150.66, 147.81, 140.63, 136.56, 131.08,
130.61, 130.37, 129.34, 127.99, 120.32, 119.67, 119.20, 118.13,
111.62, 110.60, 103.03, 68.42, 56.08, 53.66, 46.61, 41.85, 29.58,
26.27, 25.08, 25.20; ESIMS: m/z 506 (M+).
5.27. 2-[1-(3-[(11aS)-7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-
1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl]oxyhexyl)-1,2-
dihydrobenzo[c,d]indol-2-yliden]malononitrile (11h)
5.30. 2–3-[(7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-
benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy]pentyl-1,2-
dihydro-1k6-naphtho[1,8-cd]isothiazole-1,1-dione (11k)
The compound 11h was prepared according to the method de-
scribed for the compound 11a, employing the compound 10h
(669 mg, 1.0 mmol). The crude product was purified by column
chromatography (MeOH/CHCl3, 2%) to afford the compound 11h
The compound 11k was prepared according to the method
described for the compound 11a, employing the compound
10k (643 mg, 1.0 mmol). The crude product was purified by
column chromatography (MeOH/CHCl3, 2%) to afford the
compound 11k as a white solid (384 mg, 74% yield). Mp 74–
as a white solid (343 mg, 63% yield). Mp 86–91 °C; ½a D27
ꢃ
+54.4
8.02 (d, 1H,
(c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz):
d
80 °C; ½a 2D7
ꢃ
+34.1 (c = 0.5, CHCl3); 1H NMR (CDCl3, 300 MHz): d
J = 6.7 Hz), 7.94 (d, 1H, J = 7.3 Hz), 7.68 (t, 1H, J = 6.7 Hz), 7.57 (d,
1H, J = 3.8 Hz), 7.46–7.42 (m, 3H), 6.89 (d, 1H, J = 6.7 Hz), 6.72 (s,
1H), 4.12–3.97 (m, 2H), 3.94 (t, 2H, J = 6.4 Hz), 3.88 (s, 3H), 3.82–
3.76 (m, 1H), 3.70–3.67 (m, 1H), 3.59–3.52 (m, 1H), 2.33–2.24
(m, 2H), 2.09–1.98 (m, 4H), 1.96–1.81 (m, 4H), 1.67–1.52 (m,
8.08 (d, 1H, J = 8.3 Hz), 7.94 (d, 1H, J = 6.9 Hz), 7.74 (t, 1H,
J = 7.7 Hz), 7.67 (d, 1H, J = 4.3 Hz), 7.56–7.43 (m, 3H), 6.79 (s,
1H), 6.73 (d, 1H, J = 7.1 Hz), 4.17–4.02 (m, 2H), 3.93 (s, 3H),
3.88–3.78 (m, 3H), 3.75–3.68 (m, 1H), 3.62–3.53 (m, 1H), 2.36–
2.26 (m, 2H), 2.10–1.93 (m, 6H), 1.74–1.62 (m, 2H); 13C NMR
2H); 13C NMR (CDCl3, 150 MHz):
d
162.31, 150.49, 147.74,
(CDCl3, 150 MHz): d 162.37, 150.71, 147.75, 140.58, 136.52,
146.82, 140.56, 140.12, 130.68, 129.00, 128.49, 128.41, 126.63,
125.13, 124.13, 120.51, 120.16, 115.64, 111.56, 110.42, 104.89,
68.72, 67.98, 56.17, 53. 59, 46.57, 41.92, 29.53, 28.62, 28.16,
26.76, 25.35, 24.21; ESIMS: m/z 545 (M+).
131.05, 130.62, 130.34, 129.30, 127.98, 120.13, 119.64, 119.20,
118.01, 111.56, 110.48, 102.88, 68.61, 56.09, 53.64, 46.58,
41.95, 29.55, 28.46, 27.92, 24.12, 23.48; ESIMS: m/z 520
(M++1).