594
Rehse et al.
Arch. Pharm. Chem. Life Sci. 2005, 338, 590−597
N-[(2-Phenyl)pyrimido[5,4-c]cinnolin-4-yl]-Nο,Nο-diethylpropane-
1,3-diamine (6c)
H), 9.00 (d, J ϭ 7.8 Hz, 1H, ar-10-H), 9.67 (t, J ϭ 5.7 Hz, ar-NH,
D2O exchange). MS (70 eV): m/z (%) ϭ 388 (3) [Mϩ•], 317 (19),
304 (28), 85 (16), 84 (100), 58 (61), 32 (34), 28 (99).
From 0.25 g (0.85 mmol) 5a and 1.8 g (13.8 mmol) N,N-diethylpro-
pane-1,3-diamine. Yellow crystals, mp. 88°C, yield 0.16 g (48%).
Anal. C23H26N6 (386.5). IR (KBr): ν ϭ 3356 cmϪ1; 2969; 1593;
1546; 1398; 1367; 1314; 705. 1H-NMR/400 MHz ([D6]DMSO: δ
(ppm) ϭ 1.01 (t, J ϭ 7.1 Hz, 6H, 2 ϫ CH3), 1.95 (tt, J ϭ 6.7 Hz,
2H, ar-NH-CH2-CH2-CH2), 2.55Ϫ2.56 (m, partly overlapped from
DMSO, 4H, N-(CH2-CH3)2), 2.60Ϫ2.61 (br. 2H, ar-NH-CH2-CH2-
CH2), 3.82Ϫ3.87 (m, 2H, ar-NH-CH2), 7.56Ϫ7.64 (m, 3H, ph-3,4,5-
H), 8.07 (ddd, J ϭ 7.5/7.5/1.1 Hz, 1H, ar-9-H), 8.14 (ddd, J ϭ 7.6/
7.5/1.4 Hz, 1H, ar-8-H), 8.65 (d, J ϭ 8.3 Hz, 1H, ar-7-H), 8.67Ϫ8.69
(m, 2H, ph-2,6-H), 9.01 (dd, J ϭ 8.0/0.9 Hz, 1H, ar-10-H), 9.87 (t,
J ϭ 5.6 Hz, 1H, ar-NH, D2O exchange). MS (70 eV): m/z (%) ϭ
386 (11) [Mϩ•], 287 (12), 112 (100), 86 (46).
N-[2-(4-Methoxyphenyl)-pyrimido[5,4-c]cinnolin-4-yl]-NЈ-propyl-
propane-1,3-diamine (6g)
From 0.20 g (0.62 mmol) 5c and 1.2 g (10.3 mmol) N-propylpro-
pane-1,3-diamine. Light brown needles, mp. 83°C, yield 0.22 g
(87%). Anal. C23H26N6O (402.5). IR (KBr): ν ϭ 1593 cmϪ1; 1575;
1546; 1402; 1308; 1251; 1164; 769. 1H-NMR/400 MHz
([D6]DMSO): δ (ppm) ϭ 0.86 (t, J ϭ 7.4 Hz, 3H, NH-CH2-CH2-
CH3), 1.39Ϫ1.48 (m, 2H, NH-CH2-CH2-CH3), 1.92 (tt, J ϭ 6.5 Hz,
2H, ar-NH-CH2-CH2-CH2), 2.47 (t, partly overlapped by DMSO,
J ϭ 7.1 Hz, 2H, NH-CH2-CH2-CH3), 2.69 (t, J ϭ 6.4 Hz, 2H, ar-
NH-CH2-CH2-CH2), 3.86Ϫ3.88 (m, 5H, ar-NH-CH2, OCH3), 7.12
(d, J ϭ 8.8 Hz, 2H, ph-3,5-H), 8.06 (dd, J ϭ 7.6/7.2 Hz, 1H, ar-9-
H), 8.12 (dd, J ϭ 7.3/7.1 Hz, 1H, ar-8-H), 8.61Ϫ8.64 (m, 3H, ar-7-
H, ph-2,6-H), 8.99 (d, J ϭ 8.0 Hz, 1H, ar-10-H), 9.76 (br, s, 1H, ar-
NH, D2O exchange). MS (EI, 70°C): m/z (%) ϭ 402 (14) [Mϩ•],
331 (13), 317 (18), 306 (20), 305 (100), 304 (38), 126 (11), 98 (30),
30 (17), 28 (16).
N-Cyclohexyl-NЈ-[(2-phenyl)-pyrimido[5,4-c]cinnolin-4-yl]pro-
pane-1,3-diamine (6d)
From 0.12 g (0.41 mmol) 5a and 1.4 g (8.9 mmol) N-cyclohexylpro-
pane-1,3-diamine. Light yellow crystals, mp. 131°C, yield 0.16 g
(95%). Anal. C25H28N6 (412.5). IR (KBr): ν ϭ 3360 cmϪ1; 2927;
2851; 1593; 1576; 1545; 1449; 1397; 1364; 1317; 1299; 707. 1H-
NMR/400 MHz ([D6]DMSO): δ (ppm) ϭ 0.96Ϫ1.04 (m, 2H, cyc-
3a,5a-H), 1.09Ϫ1.23 (m, 3H, cyc-3e,4a,5e-H), 1.50Ϫ1.53 (m, 1H,
cyc-4e-H), 1.62Ϫ1.65 (m, 2H, cyc-2a,6a-H), 1.81Ϫ1.84 (m, 2H, cyc-
N,N-Diethyl-Nο-[(2-(4-methoxyphenyl)pyrimido[5,4-c]cinnolin-4-
yl)propane-1,3-diamine-semihydrate (6h)
2e,6e-H), 1.91 (tt,
J ϭ 6.4 Hz, 2H, ar-NH-CH2-CH2-CH2),
From 0.25 g (0.77 mmol) 5c and 1.7 g (13.1 mmol) N,N-diethylpro-
pane-1,3-diamine. Yellow crystals, mp. 138°C, yield 0.19 g (59%).
2.33Ϫ2.38 (m, 1H, cyc-1-H), 2.73 (t, J ϭ 6.1 Hz, 2H, ar-NH-CH2-
CH2-CH2), 3.88 (br, s, 2H, ar-NH-CH2), 7.59Ϫ7.63 (m, 3H, ph-
3,4,5-H), 8.08 (dd, J ϭ 7.6/7.4 Hz, 1H, ar-9-H), 8.15 (dd, J ϭ 8.2/
6.9 Hz, 1H, ar-8-H), 8.65Ϫ8.70 (m, 3H, ar-7-H, ph-2,6-H), 9.03 (d,
J ϭ 8.0 Hz, 1H, ar-10-H), 9.93 (s, 1H, ar-NH, D2O exchange). MS
(70 eV): m/z (%) ϭ 412 (6) [Mϩ•], 287 (12), 276 (16), 275 (100), 274
(19), 138 (57), 56 (18), 30 (15).
Anal. C24H28N6O Ϯ 0.5 H2O (425.5). IR (KBr): ν ϭ 3438 cmϪ1
;
3339; 1599; 1576, 1547; 103; 1308; 1257; 1166; 1H-NMR/400 MHz
([D6]DMSO): δ (ppm) ϭ 1.00 (t, J ϭ 7.0 Hz, 6H, 2 ϫ CH3), 1.92
(tt, J ϭ 6.7 Hz, 2H, ar-NH-CH2-CH2-CH2), 2.53Ϫ2.55 (partly over-
lapped by the DMSO peak, m, 4H, N-(CH2-CH3)2), 2.59 (t, J ϭ
6.6 Hz, 2H, ar-NH-CH2-CH2-CH2), 3.81Ϫ3.86 (m, 2H, ar-NH-
CH2), 3.88 (s, 3H, OCH3), 7.11 (d, J ϭ 8.8 Hz, 2H, ph-3,5-H),
8.04Ϫ8.08 (m, 1H, ar-9H), 8.13 (ddd, J ϭ 7.3/7.1/1.2 Hz, 1H, ar-8-
H), 8.61Ϫ8.65 (m, 3H, ar-7-H, ph-2,6-H), 8.99 (d, J ϭ 7.9 Hz, 1H,
ar-10-H), 9.77 (t, J ϭ 5.5 Hz, 1H, ar-NH, D2O exchange).
(CF3COOD): δ (ppm) ϭ 1.49 (t, J ϭ 7.3 Hz, 6H, 2 ϫ CH3),
2.60Ϫ2.64 (m, 2H, ar-NH-CH2-CH2-CH2), 3.41Ϫ3.52 (m, 4H, N-
(CH2-CH3)2), 3.58Ϫ3.62 (m, 2H, ar-NH-CH2-CH2-CH2), 4.11 (s,
3H, OCH3), 4.40 (t, J ϭ 7.0 Hz, 2H, ar-NH-CH2), 7.32 (d, J ϭ 9.1
Hz, 2H, ph-3,5-H), 8.54Ϫ8.57 (m, 3H, ar-9-H, ph-2,6-H), 8.67 (dd,
J ϭ 8.2/7.7 Hz, 1H, ar-8-H), 8.89 (d, J ϭ 8.7 Hz, 1H, ar-7-H), 9.28
(d, J ϭ 8.6 Hz, 1H, ar-10-H). MS (70 eV): m/z (%) ϭ 416 (15)
[Mϩ•], 317 (12), 304 (10), 113 (10), 112 (100), 86 (41), 28 (13).
2-[(3-[(2-Phenyl)-pyrimido[5,4-c]cinnolin-4-yl]aminopropyl)-
amino]ethanol (6e)
From 0.19 g (0.65 mmol) 5a and 1.1. g (9.3 mmol) [2-(3-aminoprop-
yl)amino]ethanol. Light green crystals, mp. 198°C (ethylacetate/
DMF), yield 0.14 g (57%). Anal. C21H22N6O (374.5). IR (KBr):
ν ϭ 3412 cmϪ1; 3342; 1597; 1581; 1547; 1401; 1316. 1H-NMR/400
MHz (D6]DMSO): δ (ppm) ϭ 1.91Ϫ1.97 (tt, J ϭ 6.6 Hz, 2H, ar-
NH-CH2-CH2-CH2), 2.62 (t, J ϭ 5.8 Hz, 2H, ar-NH-CH2-CH2-
CH2), 2.74 (t, J ϭ 6.6 Hz, NH-CH2-CH2-OH), 3.49Ϫ3.50 (br, m,
2H, NH-CH2-CH2-OH), 3.87Ϫ3.89 (m, 2H, ar-NH-CH2), 4.45 (s,
1H, OH, D2O exchange), 7.56Ϫ7.62 (m, 3H, ph-3,4,5-H), 8.08 (ddd,
J ϭ 8.0/7.0/1.1 Hz, 1H, ar-9-H), 8.14 (ddd, J ϭ 7.7/7.5/1.4 Hz, 1H,
ar-8-H), 8.65 (d, J ϭ 8.4 Hz, 1H, ar-7-H), 8.67Ϫ8.71 (m, 2H, ph-
2,6-H), 9.02 (dd, J ϭ 8.1/1.1 Hz, 1H, ar-10-H), 9.85 (s, 1H, ar-NH,
D2O exchange). MS (70 eV): m/z (%) ϭ 374 (10) [Mϩ•], 301 (18),
300 (20), 287 (23), 276 (23), 275 (100), 274 (37), 126 (13), 100 (27),
43 (11).
N-Cyclohexyl-NЈ-[2-(4-Methoxyphenyl)-pyrimido[5,4-c]cinnolin-4-
yl]propane-1,3-diamine (6i)
From 0.40 g (1.24 mmol) 5c and 2.5 g (15.9 mmol) N-cyclohexylpro-
pane-1,3-diamine. Yellow crystals, mp. 155°C, yield 0.31 g (56%).
Anal. C26H30N6O (442.6). IR (KBr). ν ϭ 2927 cmϪ1; 1595; 1575;
1546, 1403; 1375; 1309; 1251; 1164; 769. 1H-NMR/400 MHz
N-[(2-(4-Methoxyphenyl)pyrimido[5,4-c]cinnolin-4-yl]-NЈ,NЈ-di-
methylpropane-1,3-diamine (6f)
([D6]DMSO):
δ (ppm) ϭ 0.96Ϫ1.08 (m,, 2H, cyc-3a,5a-H),
1.09Ϫ1.22 (m, 3H, cyc-3e,4a,5e-H), 1.51Ϫ1.53 (m, 1H, cyc-4e-H),
1.62Ϫ1.65 (m, 2H, cyc-2a,6a-H), 1.90 (tt, J ϭ 6.5 Hz, 2H, ar-NH-
CH2-CH2-CH2), 2.33Ϫ2.39 (m, 1H, cyc-1H), 2.73 (t, J ϭ 6.4 Hz,
2H, ar-NH-CH2-CH2-CH2), 3.85Ϫ3.89 (m, 5H, ar-NH-CH2,
OCH3), 7.12 (d, J ϭ 8.9 Hz, 2H, ph-3,5-H), 8.06 (ddd, J ϭ 7.6/7.4/
0.8 Hz, 1H, ar-9-H), 8.12 (ddd, J ϭ 7.7/7.5/1.3 Hz, 1H, ar-8-H),
8.62Ϫ8.64 (m, 3H, ar-7-H, ph-2,6-H), 8.99 (dd, J ϭ 7.6/0.9 Hz, 1H,
ar-10-H), 9.82 (s, 1H, ar-NH, D2O exchange). MS (70 eV): m/z
(%) ϭ 442 (9) [Mϩ•], 317 (13), 306 (21), 305 (100), 304 (25), 138
(37), 56 (20), 30 (18), 28 (33).
From 0.20 g (0.62 mmol) 5c and 1.5 g (14.7 mmol) N,N-dimeth-
ylpropane-1,3-diamine. Light yellow crystals (ethanol), mp. 172°C,
yield 0.14 g (58%). Anal. C22H24N6O (3.88.5). IR (KBr): ν ϭ 3476
cmϪ1; 3423; 1595; 1576; 1547; 1404; 1309; 1253; 1165; 768. 1H-
NMR/400 MHz ([D6]DMSO): δ (ppm) ϭ 1.91 (tt, J ϭ 6.7 Hz, 2H,
ar-NH-CH2-CH2-CH2), 2.22 (s, 6H, 2 ϫ CH3), 2.45 (t, J ϭ 6.8 Hz,
2H, ar-NH-CH2-CH2-CH2), 3.80Ϫ3.85 (m, 2H, ar-NH-CH2), 7.13
(d, J ϭ 8.9 Hz, 2H, ph-3,5-H), 8.06 (dd, J ϭ 8.0/7.0 Hz, 1H, ar-9-
H), 8.11Ϫ8.14 (m, 1H, ar-8-H), 8.61Ϫ8.65 (m, 1H, ph-2,6-H, ar-7-
2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim