574 V. Tiwari et al.
moiety), 1415 (C=C, ring skeleton oxazine moiety), 1246
(C–N, str, ring skeleton oxazine moiety), 853 (C–Cl, het-
erocyclic moiety); 1H-NMR(DMSO-d6, δ): 2.31 (2H, s,
–NH2), 5.21 (1H, d, 6-H), 6.31 (1H, d, H), 7.21-8.08 (m,
10H, aromatic). Anal. Calcd: C19H14ClN3O: C, 67.94; H,
4.21; N, 12.44. Found: C, 67.98; H, 4.25; N, 12.46.
(C=C, ring skeleton oxazine moiety), 1246 (C–N, str),858
(C–Cl); 1H NMR(DMSO-d6, δ): 2.34 (3H, s, CH3), 2.32 (2H,
s, -NH2), 5.16 (1H, d, 6-H), 6.23 (1H, d, 4-H), 7.02–8.08
(m, 9H, aromatic). Anal. Calcd.: C20H16ClN3O: C, 68.58; H,
4.60; N, 12.02. Found: C, 68.61; H, 4.58; N, 12.01.
6-(2-chloroquinolin-3-yl)-4-(4-bromophenyl)-6H-1,3-oxazin-
2-amine (4f)
6-(2-Chloroquinolin-3-yl)-4-(2,4-dichlorophenyl)-6H-1,3-
oxazin-2-amine (4b)
Prepared by above method from 4f (4 mmol, 1.20 g) and
5 (4 mmol, 0.55 g) after 10-h reflux; yield: 1.66g, 98%;
brown solid. mp: 158–160°C. Rf = 0.61 in EtOAc/hexane,
4:6; ESI-MS (M+):, calcd.: 412.945, observed: 412.992; IR
(KBr, cm−1): 3410 (–NH2), 1393 (Ar–C–O), 1569 (C=C, ring
skeleton Ar moiety), 1418 (C=C, ring skeleton oxazine
moiety), 1246 (C–N, str), 858 (C–Cl), 588 (C–Br); 1H-
NMR(DMSO-d6, δ): 2.02 (2H, s, –NH2), 5.19 (1H, d, 6-H),
6.32 (1H, d, 4-H), 7.19-8.08 (m, 9H, aromatic). Anal.
Calcd.: C19H13ClBrN3O: C, 55.08; H, 3.16; N, 10.12. Found:
C, 55.16; H, 3.18; N, 10.18.
Prepared by above method from 4b (4 mmol, 0.89 g)
and 5 (4 mmol, 0.55 g) after 10 h reflux; yield: 1.34 g,
98%; brown amorphous solid. mp: 145–150°C; Rf = 0.56
in EtOAc/hexane, 3:7; ESI-MS (M+): caltd.:403.139,
observed: 403.312; IR (KBr, cm−1): 3400 (–NH2), 1396
(Ar–C–O), 1572 (C=C, ring skeleton phenyl and hetero-
cyclic moiety), 1415 (C=C, ring skeleton oxazine moiety),
1246 (C–N, str, ring skeleton oxazine moiety),858 (C–Cl,
heterocyclic moiety); 1H-NMR (DMSO-d6, δ): 2.32 (2H, s,
–NH2), 5.19 (1H, d, 6-H), 6.21 (1H, d, 4H), 7.10–8.08 (m,
8H, aromatic). Anal. Calcd: C19H12Cl3N3O: C, 56.34; H,
2.92; N, 10.43. Found: C, 56.38; H, 2.99; N, 10.46.
6-(2-Chloroquinolin-3-yl)-4-(2-bromophenyl)-6H-1,3-oxazin-
2-amine (4g)
6-(2-Chloroquinolin-3-yl)-4-(3,4-dichlorophenyl)-6H-1,3-
oxazin-2-amine (4c)
Prepared by above method from 4g (4 mmol, 1.25 g) and
5 (4 mmol, 0.54 g) after 10-h reflux; yield: 1.68 g, 97%; dark
brown solid. mp: 184–186°C; Rf = 0.68 in EtOAc/hexane,
3:7; ESI-MS (M+):, calcd.: 412.935, observed: 412.982; IR
(KBr, cm−1): 3418 (–NH2), 1393 (Ar–C–O), 1569 (C=C, ring
skeleton Ar moiety), 1418 (C=C, ring skeleton oxazine
moiety), 1246 (C–N, str), 858 (C–Cl), 588 (C-Br); 1H-NMR
(DMSO-d6, δ): 2.02 (2H, s, –NH2), 5.19 (1H, d, 6-H), 6.32
(1H, d, 4-H), 7.19–8.08 (m, 9H, aromatic). Anal. Calcd:
C19H13ClBrN3O: C, 55.03; H, 3.16; N, 10.13. Found: C,
55.16; H, 3.18; N, 10.18.
Prepared by above method from 4c (4 mmol, 0.95 g) and 5
(4 mmol, 0.55 g) after 10-h reflux; yield: 1.38g, 97%; brown
amorphous solid.mp: 156–158 °C; Rf = 0.58 in EtOAc/
hexane, 3:7; ESI-MS (M+):, calcd.: 403.155, observed:
403.075; IR (KBr, cm−1): 3398 (–NH2), 1396 (Ar–C–O), 1572
(C=C, ring skeleton Ar moiety), 1415 (C=C, ring skeleton
oxazine moiety), 1246 (C–N, str),858 (C–Cl); 1H-NMR
(DMSO-d6, δ): 2.32 (2H, s, –NH2), 5.19 (1H, d, 6-H), 6.21
(1H, d, 4-H), 7.12-8.08 (m, 8H, aromatic). Anal. Calcd.:
C19H12Cl3N3O: C, 56.36; H, 2.92; N, 10.46.Found: C, 56.41;
H, 2.99; N, 10.48.
6-(2-chloroquinolin-3-yl)-4-(3-nitrophenyl)-6H-1,3-oxazin-2-
amine (4h)
6-(2-chloroquinolin-3-yl)-4-p-tolyl-6H-1,3-oxazin-2-
amine(4d)
Prepared by above method from 4h (4 mmol, 1.32 g) and
5 (4 mmol, 0.54 g) after 16-h reflux. Yield: 1.73g, 96%;
reddish yellow solid. mp: 168–172°C; Rf = 0.58 in EtOAc/
hexane, 4:6; ESI-MS (M+):, calcd.: 380.075, observed:
380.098; IR (KBr, cm−1): 3407 (–NH2), 1398 (Ar–C–O), 1565
(C=C, ring skeleton Ar moiety), 1416 (C=C, ring skeleton
oxazine moiety), 1256 (C–N, str), 858 (C–Cl), 1589 (–NO2);
1H-NMR (DMSO-d6, δ): 2.22 (2H, s, –NH2), 5.11 (1H, d,
6-H), 6.52 (1H, d, 4-H), 7.47–8.28 (m, 9H, aromatic). Anal.
Calcd: C19H13ClBrN4O3: C, 59.90; H, 3.41; N, 14.73. Found:
C, 59.96; H, 3.48; N, 14.78.
Prepared by above method from 4d (4 mmol, 0.95 g) and
5 (4 mmol, 0.55 g) after 14-h reflux; yield: 1.38g, 97%;
dark yellow crystalline solid.mp: 160–175°C; Rf = 0.52
in EtOAc/hexane, 3:7; ESI-MS (M+):, calcd.: 349.155,
observed: 349.075; IR (KBr, cm−1): 3406 (–NH2), 1393
(Ar–C–O), 1569 (C=C, ring skeleton Ar moiety), 1418
(C=C, ring skeleton oxazine moiety), 1246 (C–N, str), 858
1
(C–Cl); H-NMR (DMSO-d6, δ): 2.34 (3H, s, CH3), 2.32
(2H, s, -NH2), 5.16 (1H, d, 6-H), 6.23 (1H, d, 4-H), 7.02-
8.08 (m, 9H, aromatic).Anal.Calcd: C20H16ClN3O: C, 68.58;
H, 4.60; N, 12.02. Found: C, 68.61; H, 4.58; N, 12.01.
6-(2-Chloroquinolin-3-yl)-4-(3,4,5-trimethoxyphenyl)-6H-1,3-
oxazin-2-amine (4i)
6-(2-chloroquinolin-3-yl)-4-o-tolyl-6H-1,3-oxazin-2-amine
(4e)
Prepared by above method from 4i (4 mmol, 1.21 g) and 5
(4 mmol, 0.55 g) after 8-h reflux; yield: 1.65 g, 98%; brown
amorphous solid. mp: 184–186°C; Rf = 0.48 in EtOAc/
hexane, 3:7; ESI-MS (M+):, calcd.: 425.175, observed:
425.198; IR (KBr, cm−1): 3397 (–NH2), 1398 (Ar–C–O), 1565
(C=C, ring skeleton Ar moiety), 1416 (C=C, ring skeleton
Prepared by above method from 4e (4 mmol, 1.19 g) and
5 (4 mmol, 0.55 g) after 14-h reflux; yield: 1.57g, 95%;%;
light brown crystalline solid. mp: 173–178°C; Rf = 0.58
in EtOAc/hexane, 3:7; ESI-MS (M+):, calcd.: 349.055,
observed: 349.075; IR (KBr, cm−1): 3403 (–NH2), 1393
(Ar–C–O), 1569 (C=C, ring skeleton Ar moiety), 1418
1
oxazine moiety), 1256 (C–N, str), 858 (C–Cl); H-NMR
(DMSO-d6, δ): 2.22 (2H, s, –NH2), 5.11 (1H, d, 6-H), 6.52
Journal of Enzyme Inhibition and Medicinal Chemistry