M. T. H. Khan et al. / Bioorg. Med. Chem. 18 (2010) 4317–4327
4323
Yield: 88%, mp 231–235 °C; IR (KBr) mmax cmꢁ1: 1664 (C@O), 1603
(C@N), 1534 (C@C, conj.), 1257 (C–C), 565 (C–I): EI-MS m/z: 424
(12), 348 (3), 297 (3), 222 (96), 209 (10), 181 (5), 146 (11), 120 (11),
105 (100), 92 (14), 77 (24), 65 (5), 51 (7); 1H NMR (300 MHz, CDCl3):
d 8.4 (d, 1H, J = 7.8), 7.98 (d, 2H, J = 15), 7.85–7.81 (t, 1H, J = 8), 7.6–
7.54 (m, 4H), 7.5–7.45 (m, 3H), 7.3–7.28 (d, 2H, J = 11.5).
4.1.14. 3-Mesityl-2-phenylquinazolin-4(3H)-one (14)
2-Phenyl-4H-3,1-benzoxazine-4-one (1 g) and 2,4,6-trimethyl-
aniline in dry benzene (10 ml) was refluxed for 8 h with continu-
ous stirring. After completion of the reaction, the reaction
mixture was allowed to cool below room temperature. The precip-
itated solid upon cooling was filtered, washed with hexane, dried
and re-crystallized from ethanol. Yield: 73%, mp 210–213 °C; IR
(KBr) mmax: 2934 (C–H), 1641 (C@O), 1496 (C@C), 1255 (C–C); EI-
4.1.10. 3-(3-Aminoethyl)-2-(4-methylphenyl) quinazolin-4(3H)-
one (10)
MS m/z: 340 (M+, 12), 254 (10), 222 (60), 146 (5), 135 (100), 120
(18), 105 (58), 92 (5), 76 (20), 65 (4); 1H NMR (300 MHz, CDCl3):
d 8.7 (d, 1H, J = 8), 8.02 (d, 1H, J = 8), 7.95 (d, 2H, J = 8), 7.63–7.42
(m, 5H), 7.28 (t, 1H, J = 8), 6.96 (s, 2H), 2.3 (s, 3H), 2.2 (s, 6H).
A
mixture of 2-(4-methylphenyl)-4H-3,1-benzoxazin-4-one
(1.7 g, 0.007 mol) and excess of 1,3-diaminoethaneane (0.967 ml,
0.0143 mol) in dry toluene (15 ml) was refluxed with continuous
stirring for 6 h. After completion of the reaction (indicated by TLC),
the reaction mixture was allowed to cool to room temperature and
then poured into water. The product precipitating was filtered,
washed with hexane and thereafter by water, dried and re-crystal-
4.1.15. 3-(2-Hydroxyethyl) quinazolin-4(3H)-one (15)
A mixture of anthranilic acid (1.2 mmol), triethylorthoformate
(2.0 mmol), monoethanolamin (2 mmol) and para-toluene sulfonic
acid (5 mmol) was stirred at room temperature under argon atmo-
sphere for 1.5 h. After completion of the reaction as indicated by
TLC, the reaction mixture was poured into 5%, aq. NaHCO3 and fol-
lowed by filtering of the precipitating product. A second crop of the
product was collected from the filtrate by extracting with dichloro-
methane, and the product obtained was dried and re-crystallized
lized from benzene. Yield: 80%, mp 190–192 °C; IR (KBr) mmax
:
3421 (NH), 2951 (C–H), 1687 (C@O), 1522 (C@N), 1446 (C@C, arom),
1359 (C–H, arom. bend), 1257 (C–O, C–N), 1229 (C–C): EI-M S (m/z):
279 (M+, 14), 263 (12), 235 (16), 222 (31), 221 (51), 194 (11), 208
(26), 163 (3), 145 (100), 137 (5), 120 (32), 119 (72), 91 (62), 65
(19), 57 (26), 56 (23): 1H NMR (300 MHz, CDCl3): d 8.86 (d, 1H,
J = 8, Ar-H), 8.63 (d, 1H, J = 6, Ar-H), 7.83–7.76 (m, 2H, Ar-H), 7.57–
7.52 (t, 1H, J = 7, Ar-H),7.31 (d, 2H, J = 9, Ar-H), 7.18 (t, 1H, J = 7, Ar-
H), 4.10 (t, 2H, J = 6, CH2), 3.52 (t, 2H, J = 6), 2.49(s, 3H, CH3), 1.18(s,
2H, N–H).
from ethanol. Yield: 89%; IR (KBr) mmax: 3250 (N–H), 2825 (C–H),
1675 (C@O), 1589 (C@C), 1450 (C@C), 1275 (C–O), 1250 (C–C);
EI-MS m/z: 190 (22), 171 (4), 160 (10), 159 (12), 147 (100), 146
(690, 145 (12), 130 (46), 129 (32), 119 (10), 105 (2), 102 (17), 92
(4), 77 (27), 76 (15), 51 (6): 1H NMR (300 MHz, CDCl3): d 8.18 (d,
1H, J = 8.04), 8.05 (s, 1H), 7.72–7.67 (t, 1H, J = 8.4), 7.615 (d, 1H,
J = 7.8), 7.452–7.398 (t, 1H, J = 8.16), 4.1506–4.1184 (t, 2H,
J = 4.8), 3.99–3.975 (t, 1H, 4.5), 2.978 (b, s, 1H).
4.1.11. 3-(3-Aminopropyl)-2-(4-methylphenyl) quinazolin-
4(3H)-one (11)
A mixture of 2-(4-methylphenyl)-4H-3,1-benzoxazin-4-one (4)
and 1,3-diaminopropane (2 ml) in dry pyridine (15 ml) was re-
fluxed with continuous stirring for 6 h. After completion of the
reaction as indicated by TLC, the mixture was acidified with few
drops of HCl. The product precipitating upon cooling was filtered,
washed with hexane and then with water, dried over anhydrous
NaSO4 and re-crystallized from benzene. Yield: 91% mp 238–
4.1.16. 3-(2-Hydroxyethyl)-2-methylquinazolin-4(3H)-one (16)
A mixture of anthranilic acid (1.2 mmol), triethylorthoacetate
(2 mmol), monoethanolamin (2 mmol) and para-toluene sulfonic
acid (5 mmol) under argon atmosphere was stirred at room tem-
perature for 1 h. After completion of the reaction, the reaction mix-
ture was poured into water and extracted with dichloromethane.
Excess of solvent was evaporated under reduced pressure and
the solid left behind was re-crystallized from ethanol–water mix-
239 °C; IR (KBr) mmax: 3228 (N–H), 3005 (C–H), 1668 (C@O), 1504
(C@N), 1424 (C@C, conj.), 1311 (C–N), 1258 (C–C); EI-MS m/z:
293 (M+, 4), 267 (5), 238 (16), 202 (26), 163 (3), 137 (5), 120
(32), 119 (100), 91 (62), 65 (19), 57 (26), 56 (23), 1H NMR
(300 MHz, CDCl3): d 8.86 (d, 1H, J = 8), 8.63 (d, 1H, J = 6), 7.83–
7.76 (m, 3H), 7.57–7.52 (t, 1H, J = 7), 7.31 (d, 2H, J = 9), 7.18 (t,
1H, J = 7), 5.6 (t, 2H, NH), 3.33 (t, 2H, J = 6), 2.72 (t, 2H, J = 9),
1.79–1.61 (m, 2H).
ture. Yield: 86%; IR (KBr)
mmax: 3250 (O–H), 1664 (C@O), 1534
(C@N, C@C), 1449 (C@C, conj.), 1304 (C–O), 1255 (C–C), 757, 700,
664 (arom. @C–H, bend); EI-MS m/z: 204 (M+,28), 185 (9), 173
(13), 161 (59), 169 (100), 159 (7), 146 (5), 145 (10), 143 (13),
119 (7), 118 (7), 116 (9), 92 (2), 90 (5), 77 (13), 76 (8), 50 (3); 1H
NMR (300 MHz, CDCl3) d 8.190 (d, 1H, J = 8), 7.38–7.682 (t, 1H,
J = 7.9), 7.631 (d, 1H, J = 7.3), 7.446–7.396 (t, 1H, J = 7.7), 4.316–
4.282 (t, 2H, J = 5.07), 4.026–3.992 (t, 2H, J = 5.26), 3.22 (b, s, 1H),
2.72 (s, 3H).
4.1.12. 2-Phenyl-3-(1, 3-thiazol-2-yl) quinazolin-4(3H)-one (12)
A
mixture of 2-phenyl-4H-3,1-benzoxazine-4-one (0.3 g,
0.001345 mol) and 2-aminothiazole (0.1345 g,) was refluxed in
dry pyridine. Yield: 71%, mp 186–189 °C: IR (KBr) mmax cmꢁ1
:
4.1.17. 2-Aminobenzoyle-N-[3-(4-oxo-2-phenylquinazolin-
3(4H )-yl) propyl]benzamide (17)
1671 (C@O), 11,601 (C@N), 1520 (C@C,), 1301 (C–H, bend), 1245
(C–O), 1234 (C–C), 834, 756, 681 (C–H, arom. bend): EI-MS m/z:
305 (M+,15), 274 (6), 262 (25), 248 (21), 228 (78), 222 (100), 208
(13), 191 (10), 146 (20), 119 (100), 91 (39), 65 (13): 1H NMR
(300 MHz, CDCl3): d 8.99 (d, 1H, J = 9), 8.47 (d, 1H, J = 9), 8.04–
8.019 (m, 2H), 7.65–7.56 (m, 4H), 7.89 (t, 1H, J = 9) 7.20 (d, 1H,
J = 4), 6.88 (d, 1H, J = 3).
2-Phenyl-4H-3,1-benzoxazin-4-one (3.76 g, 28.8 mmol) and
1,2-diaminopropane (2 ml) in 30 ml dry benzene was refluxed.
Yield: 81%, mp 90 °C; IR (KBr): 3451 (N@C–OH), 3234 (N–H),
1662 (C@O), 1528 (C@O, conj.), 1444 (–C@C, conj.) 1255 (C–N,
C–O), 1164 (C–C), 757, 706, 669 (@C–H, arom. bend): EI-MS m/z:
502 (M+, 31), 425 (5), 397 (6), 263 (10), 262 (27), 254 (9), 249
(38), 236 (31), 235 (100), 224 (78), 223 (51), 120 (33), 119 (10),
105 (89), 77 (38), 1H NMR (300 MHz, CDCl3): d 11.8 (s, 2H, NH),
8.61 (d, 2H, J = 7), 8.02 (d, 2H, J = 9), 7.99 (d, 4H, J = 9), 7.557.45
(m, 8H), 6.89 (t, 2H, J = 6), 4.01 (t, 2H, 5.3), 3.58 (t, 2H, J = 6), 2.12
(m, 2H).
4.1.13. 3-Amino-2-(4-chlorophenyl)quinazolin-4(3H)-one (13)
Yield: 90%, mp 189–190 °C; IR (KBr) mmax: 3212 (N–H), 1769
(C@O), 1660 (C@N, C@C), 1245 (C–O, C–N), 1172 (C–C), 768 (C–
Cl); EI-MS m/z: 273(M+2, 50), 272(53), 271 (M+, 100), 270 (86),
257 (4), 255 (13), 243 (100), 242 (61), 214 (4), 213 (5), 202 (24),
178 (73), 90 (3), 77 (5), 76 (8), 50 (4); 1H NMR (300 MHz, CDCl3),
d 8.30 (d, 1H, J = 6), 7.79–7.77 (m, 4H), 7.57–7.44 (m, 3H), 5.05(b,
s, 2H).
4.1.18. N-(2-Phenyl-4-oxoquinazolin-3(4H)-yl)acetamide (18)
3-Amino-2-phenyl-4(3H)-quinazolinone (0.2 g, 0.85 mmol),
triethylorthoacetate (0.37 ml) and glacial acetic acid (1.0 ml) was