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7.25. N1,N1,N2-Trimethyl-(1R,2S)-cyclohexane-1,2-diamine
(33)
7.30. 11-{2-[[(1S,2R)-2-(Dimethylamino)cyclohexyl](methyl)
amino]acetyl}-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]
diazepin-6-one Dioxalate (5)
It was obtained from 27 (0.16 g, 0.64 mmol) as described for
30: quantitative yield. 1H NMR free base (CDCl3) d: 1.03–1.59
(m, 5H); 1.60–1.06 (m, 5H); 2.17 (s, 6H); 2.32 (s, 3H); 2.70–
2.83 (m, 1H).
A mixture of 32 (0.15 g, 0.96 mmol), NEt3 (0.17 mL), and 11-(2-
chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diaze-
pin-6-one (0.35 g, 1.23 mmol) in dry DMF was stirred for 48 h at
100 °C. Removal of the solvent afforded a residue that was purified
by gravity column. Eluting with CHCl3/MeOH/aqueous 28% ammo-
nia (8.0:2.0:0.2) afforded 5 as a free base that was converted into
the dioxalate salt: 8% yield. Mp 182–185 °C; 1H NMR (CD3OD) d:
1.35–2.05 (m, 5H); 2.35–2.62 (m, 3H); 2.74–2.99 (br s + m, 4H);
3.03–3.20 (m, 1H); 3.31 (s, 6H); 3.37–3.59 (m, 2H); 7.37–7.83 (m,
5H); 7.85–8.03 (m, 1H); 8.38 (br s, 1H). HRMS calcd for C23H29N5O2
407.2321, found 407.2319. Anal. Calcd for C27H33N5O10: C, 55.19;
H, 5.66; N, 11.92. Found: C, 55.13; H, 5.57; N, 11.73.
7.26. trans-1-Methylperhydroquinoxaline (34)
It was obtained as a solid from 28 (0.15 g, 0.52 mmol), follow-
ing the procedure described for 20: 90% yield. Mp 190–192 °C;
1H NMR (CDCl3) d: 1.20–1.42 (m, 4H); 1.60–1.96 (m, 5H);
2.00–2.18 (m, 1H); 2.25 (s, 3H); 2.22–2.50 (m, 1H); 2.80–3.15
(m, 4H).
7.27. cis-1-Methylperhydroquinoxaline (35)
7.31. 11-{2-[[(1R,2S)-2-(Dimethylamino)cyclohexyl](methyl)
amino]acetyl}-6,11-dihydro-5H-benzo[e]pyrido[3,2-
b][1,4]diazepin-6-one Dioxalate (6)
It was obtained as a solid from 29 (50 mg, 0.17 mmol), follow-
ing the procedure described for 20: 71% yield. Mp 188–190 °C;
1H NMR (CDCl3) d: 1.22–1.42 (m, 2H); 1.50–1.73 (m, 3H); 1.81–
1.98 (m, 2H); 2.01–2.08 (m, 4H); 2.16 (s, 3H); 2.52–2.68 (m, 1H);
2.87–3.18 (m, 2H), 3.62–3.78 (m, 1H).
A mixture of 33 (60 mg, 0.38 mmol), NEt3 (0.1 mL), and 11-(2-
chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diaze-
pin-6-one (0.16 g, 0.56 mmol) in dry DMF was stirred for 48 h at
100 °C. Removal of the solvent afforded a residue that was puri-
fied by gravity column. Eluting with CHCl3/MeOH/aqueous 28%
ammonia (8.0:2.0:0.2) afforded 6 as a free base that was con-
verted into the dioxalate salt: 11% yield. Mp 180–182 °C; 1H
NMR (CD3OD) d: 1.35–2.04 (m, 5H); 2.36–2.64 (m, 3H); 2.75–
3.01 (br s + m, 4H); 3.03–3.18 (m, 1H); 3.31 (s, 6H); 3.36–3.59
(m, 2H); 7.39–7.82 (m, 5H); 7.85–8.03 (m, 1H); 8.38 (br s, 1H).
HRMS calcd for C23H29N5O2 407.2321, found 407.2324. Anal.
Calcd for C27H33N5O10: C, 55.19; H, 5.66; N, 11.92. Found: C,
55.19; H, 5.68; N, 11.97.
7.28. 11-{2-[[(1R,2R)-2-(Dimethylamino)cyclohexyl](methyl)
amino]acetyl}-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]
diazepin-6-one Dioxalate (3)
A mixture of 30 (0.23 g, 1.47 mmol), NEt3 (0.26 mL), and 11-
(2-chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]dia-
zepin-6-one (0.55 g, 1.94 mmol) in dry DMF was stirred at room
temperature for 48 h. Removal of the solvent afforded a residue
that was purified by flash chromatography. Eluting with CHCl3/
MeOH/aqueous 28% ammonia (8.0:2.0:0.2) afforded crude
3
7.32. 11-[2-(trans-4-Methylperhydro-1-quinoxalinyl)acetyl]-
6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (7)
which was converted into the dioxalate salt: 25% yield. Mp
185–190 °C (EtOH); 1H NMR (CD3OD) d: 1.12–1.58 (m, 3H);
1.64–1.95 (m, 3H); 1.96–2.20 (m, 1H); 2.35 (br s, 1H); 2.51–
2.78 (m, 4H); 2.78–3.00 (m, 3H); 3.05–3.22 (m, 1H); 3.22–3.35
(m, 3H); 3.35–3.60 (m, 1H); 3.60–3.98 (m, 1H); 7.40–7.83 (m,
5H); 7.85–8.01 (m, 1H); 8.35–8.43 (m, 1H). HRMS calcd for
A mixture of 34 (30 mg, 0.19 mmol), NEt3 (0.05 mL), and 11-(2-
chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin
-6-one (80 mg, 0.28 mmol) in dry DMF was stirred for 48 h at 60 °C.
Removal of the solvent afforded a residue that was purified by
gravity column. Eluting with CHCl3/MeOH/aqueous 28% ammonia
(8.0:2.0:0.2) provided 7: 55% yield. Mp 185–190 °C; 1H NMR (CDCl3)
d: 1.05–1.42 (m, 8H); 1.50–1.80 (m, 2H); 1.84–2.05 (m, 2H); 2.23 (s,
3H); 2.63–2.80 (m, 1H); 2.83–2.98 (m, 1H); 3.23–3.89 (m, 1H); 4.00–
4.20 (m, 1H); 7.20–7.50 (m, 3H); 7.60–7.85 (m, 2H); 7.90–8.03 (m,
1H); 8.20–8.35 (m, 1H); 10.00 (br s, 1H). HRMS calcd for C23H27N5O2
405.2165, found 405.2161. Anal. Calcd for C23H27N5O2: C, 68.13; H,
6.71; N, 17.27. Found: C, 68.32; H, 6.51; N, 17.40.
C
C
23H29N5O2 407.2321, found 407.2318. Anal. Calcd for
27H33N5O10: C, 55.19; H, 5.66; N, 11.92. Found: C, 55.32; H,
5.45; N, 11.81.
7.29. 11-{2-[[(1S,2S)-2-(Dimethylamino)cyclohexyl](methyl)
amino]acetyl}-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]
diazepin-6-one Dioxalate (4)
It was obtained from 31 (0.29 g, 1.86 mmol), NEt3 (0.34 mL),
and
11-(2-chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-
7.33. 11-[2-(cis-4-Methylperhydro-1-quinoxalinyl)acetyl]-6,11-
dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one (8)
b][1,4]diazepin-6-one (0.70 g, 2.4 mmol) as described for 3. Re-
moval of the solvent afforded a residue that was purified first by
flash chromatography and then by gravity column. Eluting with a
step-gradient system of CHCl3/MeOH/aqueous 28% ammonia
(8.0:2.0:0.2 to 9.0:1.0:0.1) and CHCl3/MeOH/EtOAc/aqueous 28%
ammonia (3.0:4.0:3.0:0.2) afforded 4 as a free base that was con-
verted into the dioxalate salt: 11.8% yield. Mp 185–190 °C; 1H
NMR (CD3OD) d: 1.12–1.62 (m, 3H); 1.62–1.99 (m, 3H); 2.02–2.20
(m, 1H); 2.32 (br s, 1H); 2.52–2.80 (m, 4H); 2.80–2.98 (m, 3H);
3.12–3.25 (m, 1H); 3.25–3.35 (m, 3H); 3.35–3.64 (m, 1H); 3.65–
3.95 (m, 1H); 7.43–7.83 (m, 5H); 7.84–8.00 (m, 1H); 8.32–8.42 (m,
1H). HRMS calcd for C23H29N5O2 407.2321, found 407.2323. Anal.
Calcd for C27H33N5O10: C, 55.19; H, 5.66; N, 11.92. Found: C, 55.26;
H, 5.48; N, 11.75.
A mixture of 35 (19 mg, 0.12 mmol), NEt3 (0.03 mL), and 11-(2-
chloroacetyl)-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diaze-
pin-6-one (53 mg, 0.18 mmol) in dry DMF was stirred for 48 h at
60 °C. Removal of the solvent afforded a residue that was purified
by gravity column. Eluting with CHCl3/MeOH/aqueous 28% ammo-
nia (9.0:1.0:0.05) afforded 8as a wax solid: 16% yield. 1H NMR
(CDCl3) d: 1.10–1.42 (m, 8H); 1.50–1.90 (m, 2H); 1.84–2.20 (m,
2H); 2.03 (s, 3H); 3.25–3.34 (m, 2H); 3.80–4.00 (m, 2H); 7.23–
7.87 (m, 5H); 7.90–8.03 (m, 1H); 8.20–8.35 (m, 1H); 8.80 (br s,
1H). HRMS calcd for C23H27N5O2 405.2165, found 405.2169. Anal.
Calcd for C23H27N5O2: C, 68.13; H, 6.71; N, 17.27. Found: C,
68.45; H, 6.69; N, 17.31.