R.T. Iminov et al. / Tetrahedron 68 (2012) 3098e3102
3101
4.46e4.52 (2H, m, CH2Ph), 4.77 (1H, dd, J3¼6.0, J3¼7.0, 4-H), 7.27
(2H, m, HPh, 4-HAr), 7.31e7.41 (4H, m, 4HPh), 7.56 (1H, t, J¼8.0, 5-
HAr), 7.83 (1H, d, J¼8.0, 6-HAr), 8.12 (1H, d, J¼8.0, 3-HAr), 9.38 (1H,
t, J¼5.5, NHCH2), 10.33 (2H, br s, NH$HCl), 11.60 (1H, s, CONH); dC
(DMSO-d6) 33.4 (5-C), 43.2 (CH2Ph), 48.7 (2-C), 63.5 (4-C), 122.8 (6-
CAr), 124.7 (2-CAr), 124.9 (4-CAr), 127.3 (4-CPh), 127.8 (3,5-CPh), 128.8
(2,6-CPh), 128.9 (3-CAr), 132.1 (5-CAr), 137.2 (1-CAr), 139.6 (1-CPh),
165.5 (CONH), 168.1 (CONH); nmax(KBr) 3280, 1682, 1594, 1531,
1454, 1323, 1244, 750, 700 cmꢁ1; found: C, 57.29; H, 5.27; N, 11.36;
Cl, 9.57; S, 8.67. C18H19N3O2S$HCl requires C, 57.21; H, 5.33; N,11.12;
Cl, 9.38; S, 8.48.
13.9 (CH3), 25.4 (9-C), 29.2 (10-C), 36.0 (CH2CH3), 55.7 (8-C), 64.4
(10a-C), 89.6 (6a-C), 121.1 (1-C), 121.9 (4a-C), 126.0 (3-C), 128.3 (4-
C), 133.3 (2-C), 135.1 (12a-C), 161.8 (5-CO), 173.0 (11-CO);
nmax(KBr) 1723, 1647, 1489, 1468, 1422, 1304, 1190, 1096, 766,
696 cmꢁ1; found: C, 66.38; H, 6.28; N, 15.28. C15H17N3O2 requires C,
66.40; H, 6.32; N, 15.49.
3.3.3. 6-Benzyl-5,6,6a,8,9,10,10a,11-octahydro-pyrrolo[10,20:3,4]imi-
dazo[1,2-a]quinazoline-5,11-dione (8c). Yield 0.64 g (48%); White
powder; mp 166e167 ꢀC (from dioxane); dH (DMSO-d6) 1.58e1.64
(1H, m, 10-H), 1.67e1.73 (1H, m, 10-H), 1.94e1.98 (1H, m, 9-H),
2.04e2.08 (1H, m, 9-H), 2.76e2.82 (1H, m, 8-H), 2.99e3.05 (1H, m,
8-H), 3.85 (1H, dd, J¼4.0, J¼8.5, 10a-H), 4.77 (1H, d, J¼15.0, CH2Ph),
4.87 (1H, d, J¼15.0, CH2Ph), 6.03 (1H, s, 6a-H), 7.20e7.23 (1H, m,
HPh), 7.25e7.34 (4H, m, 4HPh), 7.39 (1H, t, J¼8.0, 3-H), 7.66 (1H, t,
J¼8.0, 2-H), 7.73 (1H, d, J¼8.0, 1-H), 7.97 (1H, d, J¼8.0, 4-H); dC
(DMSO-d6) 25.2 (9-C), 29.2 (10-C), 44.6 (CH2Ph), 55.6 (8-C), 64.4
(10a-C), 89.9 (6a-C), 121.2 (1-C), 121.7 (4a-C), 126.1 (3-C), 127.2 (4-
CPh), 127.8 (3,5-CPh), 128.6 (4-C), 128.9 (2,6-CPh), 133.6 (2-C), 135.3
(12a-C), 138.7 (1-CPh), 162.3 (5-CO), 172.9 (11-CO); nmax(KBr) 1715,
1697, 1649, 1637, 1489, 1429, 1417, 1404, 1320, 1233, 1138, 1089, 766,
738, 703 cmꢁ1; found: C, 71.93; H, 5.75; N, 12.60. C20H19N3O2 re-
quires C, 72.05; H, 5.74; N, 12.60.
3.2.8. N-[2-(Anilinocarbonyl)phenyl]thiazolidine-4-carboxamide hy-
drochloride (7d). Yield 2.02 g (74%); White crystals; mp 171e172 ꢀC;
dH (DMSO-d6) 3.28 (1H, dd, J2¼11.5, J3¼6.5, 5-H), 3.48 (1H, dd,
J2¼11.5, J3¼7.5, 5-H), 4.27e4.33 (2H, m, 2-CH2), 4.73 (1H, dd, J3¼6.5,
J3¼7.5, 4-H), 7.11 (1H, t, J¼7.0, 4-HPh), 7.31e7.39 (3H, m, 4-HAr, 2,6-
HPh), 7.58 (1H, t, J¼7.5, 5-HAr), 7.74e7.81 (3H, m, 6-HAr, 3,5-HPh),
7.86 (1H, d, J¼7.5, 3-HAr), 10.27 (2H, br s, NH$HCl), 10.50 (1H, s,
CONH), 11.05 (1H, s, CONH); dC (DMSO-d6) 33.6 (5-C), 49.1 (2-C),
63.6 (4-C), 120.9 (2,6-CPh), 124.0 (6-CAr), 124.3 (4-CAr), 125.4 (4-CPh),
128.4 (2-CAr), 129.1 (3,5-CPh), 129.4 (3-CAr), 131.7 (5-CAr), 135.9 (1-
CAr), 139.6 (1-CPh), 165.7 (CONH), 166.6 (CONH); nmax(KBr) 3266,
1679, 1644, 1549, 1540, 1489, 1447, 1330, 1260, 760, 745 cmꢁ1
;
found: C, 56.20; H, 4.74; N, 11.44; Cl, 9.70; S, 8.71. C17H17N3O2S$HCl
requires C, 56.12; H, 4.99; N, 11.55; Cl, 9.74; S, 8.81.
3.3.4. 6-Phenyl-5,6,6a,8,9,10,10a,11-octahydro-pyrrolo[10,20:3,4]imi-
dazo[1,2-a]quinazoline-5,11-dione (8d). Yield 0.59 g (46%); Clean
yellow oil; Rf (CHCl3/MeOH, 9:1) 0.74; dH (CDCl3) 1.69e1.78 (2H, m,
10-CH2), 2.06e2.18 (2H, m, 9-CH2), 2.73e2.77 (1H, m, 8-H),
2.79e2.84 (1H, m, 8-H), 4.02 (1H, dd, J¼5.5, J¼7.0, 10a-H), 6.14 (1H,
s, 6a-H), 7.24 (2H, d, J¼7.5, 2,6-HPh), 7.32e7.40 (2H. m. 3-H, 4-HPh),
7.46 (2H, t, J¼7.5, 3,5-HPh), 7.63 (1H, t, J¼8.0, 2-H), 7.90 (1H, d, J¼8.0,
1-H), 8.15 (1H, d, J¼8.0, 4-H); dC (CDCl3) 25.2 (9-C), 28.4 (10-C), 54.2
(8-C), 64.5 (10a-C), 90.8 (6a-C), 119.6 (1-C), 121.5 (4a-C), 125.9 (3-C),
128.3 (4-C), 128.9 (4-CPh), 129.4 (3,5-CPh), 130.1 (2,6-CPh), 133.2 (2-
C), 134.9 (12a-C), 138.4 (1-CPh),163.4 (5-CO), 172.2 (11-CO);
nmax(KBr) 1718, 1665, 1654, 1598, 1522, 1490, 1432, 1325, 750,
693 cmꢁ1; found: C, 71.32; H, 5.33; N, 13.20. C19H17N3O2 requires C,
71.46; H, 5.37; N, 13.16.
3.3. Pyrrolo[10,20:3,4]imidazo[1,2-a]quinazoline-5,11-diones
8aed and thiazolo[30,40:3,4]imidazo[1,2-a]quinazoline-5,11-
diones 9aed. General procedure
A solution of the corresponding compounds 6aed, 7aed/HCl
(4.0 mmol) and triethylamine (0.41 g, 4.0 mmol) in triethyl ortho-
formate (10 mL) was heated at reflux for 5e6 h. After cooling the
triethyl orthoformate was removed in vacuo, the residue was dis-
solved in ethyl acetate (30 mL), washed with water (2ꢂ10 mL) and
dried (Na2SO4). The extract was evaporated and the solid residue
was recrystallized from a suitable solvent to yield derivatives 8a, 8c,
9aed. In the case of compounds 8b, 8d the residue after the evap-
oration remained oily. It was taken up in CHCl3 (5 mL) and purified
by column chromatography on silica (CHCl3/MeOH, 9:1). Evapora-
tion of the appropriate fractions afforded compounds 8b, 8d.
3.3.5. 6-Methyl-5,6,6a,10,10a,11-xehahydro-thiazolo[30,40:3,4]imi-
dazo[1,2-a]quinazoline-5,11-dione (9a). Yield 0.56 g (51%); White
powder; mp 184e185 ꢀC (from acetonitrile); dH (DMSO-d6) 3.08
(3H, s, CH3), 3.33 (1H, dd, J2¼10.5, J3¼8.0, 10-H), 3.41 (1H, dd,
J2¼10.5, J3¼1.5, 10-H), 4.21 (1H, d, J¼11.0, 8-H), 4.38 (1H, dd, J¼1.5,
J¼8.0,10a-H), 4.58 (1H, d, J¼11.0, 8-H), 5.90 (1H, s, 6a-H), 7.39 (1H, t,
J¼8.0, 3-H), 7.66 (1H, t, J¼8.0, 2-H), 7.84 (1H, d, J¼8.0,1-H), 7.95 (1H,
d, J¼8.0, 4-H); dC (DMSO-d6) 27.9 (CH3), 37.1 (10-C), 61.5 (8-C), 67.7
(10a-C), 89.5 (6a-C), 120.2 (1-C), 120.8 (4a-C), 126.3 (3-C), 128.5 (4-
C), 133.6 (2-C), 134.3 (12a-C), 161.9 (5-CO), 170.4 (11-CO); nmax(KBr)
1728, 1651,1489, 1471, 1429, 1409,1374,1323, 1281,1230,1112,1045,
948, 751, 687 cmꢁ1; found: C, 56.60; H, 4.93; N, 15.38; S, 11.78.
C13H13N3O2S requires C, 56.71; H, 4.76; N, 15.26; S, 11.65.
3.3.1. 6-Methyl-5,6,6a,8,9,10,10a,11-octahydro-pyrrolo[10,20:3,4]imi-
dazo[1,2-a]quinazoline-5,11-dione (8a). Yield 0.61 g (59%); Yellow-
ish powder; mp 87e88 ꢀC (from EtOH); dH (DMSO-d6) 1.72e1.78
(1H, m, 10-H), 1.84e1.90 (1H, m, 10-H), 2.05e2.11 (1H, m, 9-H),
2.13e2.21 (1H, m, 9-H), 3.03 (3H, s, CH3), 3.06e3.10 (1H, m, 8-H),
3.21e3.27 (1H, m, 8-H), 3.95 (1H, dd, J¼5.0, J¼8.5,10a-H), 5.77 (1H, s,
6a-H), 7.28 (1H, t, J¼8.0, 3-H), 7.55 (1H, t, J¼8.0, 2-H), 7.76 (1H, d,
J¼8.0, 1-H), 7.93 (1H, d, J¼8.0, 4-H); dC (DMSO-d6) 25.3 (9-C), 27.9
(CH3), 29.3 (10-C), 55.5 (8-C), 64.4 (10a-C), 90.5 (6a-C), 120.9 (1-C),
121.4 (4a-C),126.0 (3-C),128.3 (4-C),133.3 (2-C),135.1 (12a-C),162.4
(5-CO), 172.8 (11-CO); nmax(KBr) 2928, 2853, 1743, 1724, 1655, 1489,
1473, 1339, 1320, 1191, 1092, 796, 774, 701 cmꢁ1; found: C, 65.36; H,
5.65; N, 16.29. C14H15N3O2 requires C, 65.36; H, 5.88; N, 16.33.
3.3.6. 6-Ethyl-5,6,6a,10,10a,11-xehahydro-thiazolo[30,40:3,4]imidazo
[1,2-a]quinazoline-5,11-dione (9b). Yield 0.68
g (59%); White
powder; mp 188, 189 ꢀC (from toluene); dH (DMSO-d6) 1.20 (3H, t,
J¼6.0, CH3), 3.33 (1H, dd, J2¼12.0, J3¼7.0, 10-H), 3.42 (1H, dd,
J2¼12.0, J3¼1.0, 10-H), 3.56e3.60 (1H, m, CH2CH3), 3.70e3.74 (1H,
m, CH2CH3), 4.25 (1H, d, J¼12.0, 8-H), 4.41 (1H, dd, J¼7.0, J¼1.0,
10a-H), 4.59 (1H, d, J¼12.0, 8-H), 6.08 (1H, s, 6a-H), 7.39 (1H, t,
J¼8.0, 3-H), 7.66 (1H, t, J¼8.0, 2-H), 7.77 (1H, d, J¼8.0, 1-H), 7.95
(1H, d, J¼8.0, 4-H); dC (DMSO-d6) 14.1 (CH3), 36.2 (CH2CH3), 36.9
(10-C), 61.7 (8-C), 67.8 (10a-C), 89.1 (6a-C), 120.5 (1-C), 121.4 (4a-
C), 126.3 (3-C), 128.4 (4-C), 133.6 (2-C), 134.2 (12a-C), 161.4 (5-CO),
170.4 (11-CO); nmax(KBr) 2928, 2853, 1748, 1734, 1716, 1697, 1683,
3.3.2. 6-Ethyl-5,6,6a,8,9,10,10a,11-octahydro-pyrrolo[10,20:3,4]imi-
dazo[1,2-a]quinazoline-5,11-dione (8b). Yield 0.61
g (56%); Rf
(CHCl3/MeOH, 9:1) 0.90; Yellowish powder; mp 92e93 ꢀC; dH
(DMSO-d6) 1.16 (3H, t, J¼7.0, CH3), 1.70e1.74 (1H, m, 10-H),
1.79e1.85 (1H, m, 10-H), 1.98e2.04 (1H, m, 9-H), 2.12e2.16 (1H, m,
9-H), 3.06e3.11 (1H, m, 8-H), 3.19e3.25 (1H, m, 8-H), 3.58e3.62
(1H, m, CH2CH3), 3.65e3.69 (1H, m, CH2CH3), 4.00e4.04 (1H, m,
10a-H), 6.07 (1H, s, 6a-H), 7.37 (1H, t, J¼8.0, 3-H), 7.64 (1H, t, J¼8.0,
2-H), 7.72 (1H, d, J¼8.0, 1-H), 7.94 (1H, d, J¼8.0, 4-H); dC (DMSO-d6)
1669, 1653, 1489, 1473, 1427, 1390, 1122, 756, 724, 687 cmꢁ1
;