V. Alagarsamy, U. S. Pathak / Bioorg. Med. Chem. 15 (2007) 3457–3462
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wise under constant stirring. The solution was stirred
further at room temperature for 12 h. The solid obtained
was filtered, washed with cold water, dried and recrys-
tallized from chloroform/ethanol (50:50), yield = 91%,
(CDCl3): d 5.5 (s, 2H, N–CH2), 5.9 (s, 2H, CH2-Cl),
7.4–8.3 (m, 9H, ArH); IR (KBr) cmꢀ1: 1685 (C@O);
MS m/z: 324 (M+); Anal. Calcd for C17H13N4OCl: C,
62.87; H, 04.03; N, 17.25. Found: C, 62.91; H, 04.07; N,
17.29.
1
mp 155–159 °C; H NMR (DMSO-d6): d 2.51 (s, 3H,
SCH3), 6.6 (s, 2H, NH2, D2O exchangeable), 7.5–7.8
(m, 4H, ArH); IR (KBr) cmꢀ1: 3400, 3320 (NH2),
1700 (C@O); MS m/z: 207 (M+); Anal. Calcd for
C8H9N3OS: C, 52.15; H, 04.37; N, 20.27. Found: C,
52.10; H, 04.39; N, 20.31.
4.1.8. 3-Benzyl-2-(morphlinyl methyl)-3H-[1,2,4]triazolo-
[5,1-b] quinazolin-9-one (7e). A mixture of 7d (0.01 mol),
morpholine (0.05 mol) and anhydrous potassium carbon-
ate (100 mg) in dioxane (15 ml) was refluxed on an oil bath
for 30 h. Then the reaction mixture was poured into
crushed ice, the solid obtained was filtered, washed
with water, dried and recrystallized from benzene/metha-
nol (50:50). Yield = 80%, mp 200–203 °C; 1H NMR
(CDCl3): d 3.4 (m, 4H, –N(CH2CH2)2O–), 3.9 (m, 4H,
–N(CH2CH2)2O–), 4.84 (s, 2H, N–CH2), 5.4 (s, 2H,
CH2), 7.1–8.0 (m, 9H, ArH); IR (KBr) cmꢀ1: 1693
(C@O); MS m/z: 375 (M+); Anal. Calcd for
C21H21N5O2: C, 67.18; H, 05.63; N, 18.65. Found: C,
67.26; H, 5.65; N, 18.62. Adopting this procedure com-
pound 7f was prepared.
4.1.3. 3-Amino-2-benzylamino-3H-quinazolin-4-one (6). A
mixture of benzylamine (0.05 mol) and 3-amino-2-meth-
ylsulfanyl-3H-quinazolin-4-one (5) (0.01 mol) was heated
at 80 °C on an oil bath for 36 h. The reaction mixture
was cooled and triturated with petroleum ether (60–
80), the separated solid was filtered and recrystallized
1
from ethanol. Yield = 72%, mp 168–170 °C; H NMR
(CDCl3): d 4.3 (t, 1H, NH, D2O exchangeable), 4.9 (s,
2H, CH2), 5.3 (s, 2H, NH2), 7.4–8.4 (m, 9H, ArH); IR
(KBr) cmꢀ1: 3400, 3350 (NH2), 1680 (C@O); MS m/z:
266 (M+); Anal. Calcd for C15H14N4O: C, 67.65; H,
05.29; N, 21.03. Found: C, 67.61; H, 5.36; N, 21.07.
4.1.9. 3-Benzyl-2-(piperidyl methyl)-3H-[1,2,4]triazolo-
[5,1-b] quinazolin-9-one (7f). The title compound was
prepared from 7d and piperidine in 50% yield. Mp
189–190 °C; 1H NMR (CDCl3): d 1.6–1.9 (m, 6H,
4.1.4. 3-Benzyl-3H-[1,2,4]triazolo[5,1-b]quinazolin-9-one
(7a). A mixture of 6 (0.01 mol) and formic acid (15 ml)
was refluxed on an oil bath for 6 h. The reaction mixture
was then poured into crushed ice, the solid separated
was filtered, washed with water, dried and recrystallized
–NCH2CH2CH2-piperidinyl),
2.0–2.2
(m,
4H,
–NCH2CH2-piperidinyl), 4.3 (s, 2H, –N–CH2-piperidi-
nyl), 5.1 (s, 2H, CH2), 7.8–8.4 (m, 9H, ArH); IR
(KBr) cmꢀ1: 1690 (C@O); MS m/z: 373 (M+); Anal.
Calcd for C22H23N5O: C, 70.75; H, 06.20; N, 18.75.
Found: C, 70.81; H, 06.29; N, 18.74.
1
from ethanol. Yield = 94%, mp 224–225 °C; H NMR
(CDCl3): d 5.3 (s, 2H, CH2), 5.5 (s, 1H, CH), 7.7-8.0
(m, 9H, ArH); IR (KBr) cmꢀ1: 1700 (C@O); MS m/z:
276 (M+); Anal. Calcd for C16H12N4O: C, 69.55; H,
04.37; N, 20.27. Found: C, 69.51; H, 04.41; N, 20.29.
The following compounds 7b and 7c were prepared
using a similar procedure to that described for 7a.
4.1.10. 3-Benzyl-2-phenyl-3H-[1,2,4]triazolo[5,1-b]quinazo-
lin-9-one (7g). A mixture of 6 (0.01 mol) and phenyl isothi-
ocyanate (0.01 mol) in dimethylformamide (10 ml) was
refluxed on an oil bath for 12 h. The reaction mixture
was cooled, poured into ice water and the solid separated
was filtered, dried and recrystallized from benzene/metha-
nol (50:50). Yield = 38%, mp 216–218 °C; 1H NMR
(CDCl3): d 4.5 (s, 1H, NH), 5.4 (s, 2H, CH2), 7.1–8.2
(m, 14H, ArH); IR (KBr) cmꢀ1: 3380 (NH), 1680
(C@O); MS m/z: 367 (M+); Anal. Calcd for C22H17N5O:
C, 71.92; H, 04.66; N, 19.06. Found: C, 71.86; H, 04.71;
N, 19.09. Using this procedure compounds 7h–7j were
prepared.
4.1.5.
3-Benzyl-2-methyl-3H-[1,2,4]triazolo[5,1-b]quin-
azolin-9-one (7b). The title compound was prepared
from 6 and acetic acid in 95% yield. Mp 221–223 °C;
1H NMR (CDCl3): d 2.3 (s, 3H, CH3), 4.9 (s, 2H,
CH2), 7.2–8.3 (m, 9H, ArH); IR (KBr) cmꢀ1: 1680
(C@O), MS m/z: 290 (M+); Anal. Calcd for
C17H14N4O: C, 70.33; H, 04.86; N, 19.29. Found: C,
70.35; H, 04.83; N, 19.33.
4.1.6.
3-Benzyl-2-propyl-3H-[1,2,4]triazolo[5,1-b]quin-
azolin-9-one (7c). The title compound was prepared
from 6 and butyric acid in 88% yield. Mp 135–137 °C;
1H NMR (CDCl3) d 1.1–1.2 (t, 3H, CH2CH2CH3),
1.7–1.8 (sext, 2H, CH2CH2CH3), 2.8–2.9 (t, 2H,
CH2CH2CH3), 3.7 (s, 2H, CH2), 7.6–8.2 (m, 9H,
ArH); IR (KBr) cmꢀ1: 1690 (C@O); MS m/z: 318
(M+); Anal. Calcd for C19H18N4O: C, 71.67; H, 05.69;
N, 17.59 Found: C, 71.74; H, 5.72; N, 17.57.
4.1.11. 3-Benzyl-2-(4-methylphenyl)-3H-[1,2,4]triazolo[5,1-
b] quinazolin-9-one (7h). The title compound was pre-
pared from 6 and 4-methylphenyl isothiocyanate in
40% yield. Mp 205–207 °C; 1H NMR (CDCl3): d 2.7
(s, 3H, CH3), 4.0 (s, 1H, NH), 4.9 (s, 2H, CH2), 7.0–
8.5 (m, 13H, ArH); IR (KBr) cmꢀ1: 3320 (NH), 1686
(C@O); MS m/z: 381 (M+); Anal. Calcd for
C23H19N5O: C, 72.42; H, 05.02; N, 18.35. Found: C,
72.51; H, 05.09; N, 18.37.
4.1.7. 3-Benzyl-2-chloromethyl-3H-[1,2,4]triazolo[5,1-b]qui-
nazolin-9-one (7d). A mixture of 6 (0.01 mol) and chloro-
acetylchloride (0.01 mol) in glacial acetic acid (15 ml) was
refluxed on an oil bath for 8 h, the reaction mixture was
then poured into crushed ice and the solid separated
was filtered, washed with water, dried and recrystallized
4.1.12. 3-Benzyl-2-(4-methoxyphenyl)-3H-[1,2,4]triazolo-
[5,1-b] quinazolin-9-one (7i). The title compound was
prepared from 6 and 4-methoxyphenyl isothiocyanate
in 38% yield. Mp 260–262 °C; 1H NMR (CDCl3): d
2.8 (s, 3H, OCH3), 4.2 (s, 1H, NH), 4.7 (s, 2H, CH2),
7.7–8.9 (m, 13H, ArH); IR (KBr) cmꢀ1: 3290 (NH),
1
from ethanol. Yield = 79%, mp 212–215 °C; H NMR