3052
V. Chandregowda et al. / European Journal of Medicinal Chemistry 44 (2009) 3046–3055
The reaction mass was cooled to RT, filtered and organic solvent
was concentrated under vacuum. The residue obtained was dis-
solved in ethyl acetate and washed with water. Finally organic
solvent was dried over sodium sulphate and concentrated to obtain
crude material, which was further purified by column chromatog-
raphy to get pure material of title compounds 18–36 with yields
ranging from 60 to 75%.
1427, 1515, 1577, 1627, 2927, 3100, 3300 cmꢂ1
200 MHz):
;
1H NMR (CDCl3,
2.35 (s, 3H), 2.44 (m, 2H), 3.57 (t, J ¼ 6.6 Hz, 2H), 3.98
d
(s, 3H), 4.23 (t, J ¼ 6.2 Hz, 2H), 7.08 (s, 1H), 7.20 (d, J ¼ 8.4 Hz, 2H),
7.22 (s, 1H), 7.29–7.39 (m, 3H), 7.51 (d, J ¼ 8.4 Hz, 2H), 7.69–7.80 (m,
2H); 13C NMR (CDCl3, 200 MHz):
d 20.42, 28.37, 29.74, 55.62, 66.56,
100.97, 107.20, 108.32, 120.47, 120.89, 122.05, 123.93, 125.65, 129.06,
133.38, 134.50, 135.55, 145.25, 146.80, 147.30, 153.20, 154.60, 156.21,
163.00; GC–MS (m/z): 488 (Mþ).
4.1.5.1. 6-[3-(Benzothiazol-2-ylthio)propoxy]-N-(3-chloro-4-fluoro-
phenyl)-7-methoxyquinazo-lin-4-amine (18). Using 10 and 47 as
starting materials, compound 18 was obtained as pale yellow solid
in 70% yield; m.p. 173–176 ꢀC; IR (KBr): 756, 848, 995, 1064, 1145,
1211, 1242, 1346, 1473, 1504, 1577, 1624, 2923, 3128, 3301 cmꢂ1; 1H
4.1.5.6. 6-[3-(Benzoxazol-2-ylthio)propoxy]-N-(3-chloro-4-fluoro-
phenyl)-7-methoxy-quinazolin-4-amine (23). Using 10 and 48 as
starting materials, compound 23 was obtained as pale yellow solid
in 70% yield; m.p. 63–67 ꢀC; IR (KBr): 547, 744, 852, 1002, 1068,
1134, 1251, 1334, 1427, 1500, 1577, 1624, 2927, 3070, 3300 cmꢂ1; 1H
NMR (CDCl3, 200 MHz):
d
2.37 (m, 2H), 3.52 (t, J ¼ 6.6 Hz, 2H), 3.97
(s, 3H), 4.17 (t, J ¼ 5.8 Hz, 2H), 7.08–7.17 (m, 2H), 7.32–7.39 (m, 3H),
NMR (CDCl3, 200 MHz):
d
2.42 (m, 2H), 3.50 (t, J ¼ 6.6 Hz, 2H), 3.98
7.47–7.53 (m, 1H), 7.62 (br s, 1H), 7.02–7.88 (m, 3H), 8.65 (s, 1H); 13C
(s, 3H), 4.21 (t, J ¼ 6.2 Hz, 2H), 7.09–7.18 (m, 2H), 7.21–7.24 (m, 3H),
7.38–7.40 (m, 1H), 7.50–7.57 (m, 3H), 7.90 (m, 1H), 8.66 (s, 1H);
HRMS (m/z): Calculated for C25H20N4O3SFCl (M þ H)þ ¼ 511.1007,
found ¼ 511.1022.
NMR (CDCl3, 200 MHz): d 28.94, 30.48, 56.24, 67.22, 100.88, 108.16,
117.20, 117.65, 121.05, 121.49, 121.60, 124.09, 124.60, 126.26, 135.95,
147.95, 148.80, 152.00,153.00,153.50,155.50,156.00,157.50,165.00,
166.50; GC–MS (m/z): 527 (Mþ).
4.1.5.7. 6-[3-(Benzoxazol-2-ylthio)propoxy]-7-methoxy-N-[3-(trifluoro-
methyl)phenyl]quinazolin- 4-amine (24). Using 9 and 48 as starting
materials, compound 24 was obtained as off-white solid in 70%
yield; m.p. 147–149 ꢀC; IR (KBr): 586, 744, 848, 1006, 1068, 1118,
1238, 1326, 1446, 1504, 1581, 1624, 2927, 3012, 3300 cmꢂ1; 1H NMR
4.1.5.2. 6-[3-(Benzothiazol-2-ylthio)propoxy]-7-methoxy-N-[3-(tri-
fluoromethyl)phenyl]quinazo-lin-4-amine (19). Using 9 and 47 as
starting materials, compound 19 was obtained as off-white solid in
70% yield; m.p. 92–95 ꢀC; IR (KBr): 756, 848, 995, 1064, 1122, 1234,
1326, 1427, 1450, 1508, 1581, 1627, 2927, 3282 cmꢂ1
;
1H NMR
2.41 (m, 2H), 3.55 (t, J ¼ 6.6 Hz, 2H), 3.98 (s,
3H), 4.23 (t, J ¼ 6 Hz, 2H), 7.15–7.53 (m, 6H), 7.69–7.79 (m, 3H), 7.94–
8.01 (m, 2H), 8.68 (s,1H); 13C NMR (CDCl3, 200 MHz):
28.33, 29.83,
(CDCl3, 200 MHz):
d
2.42 (m, 2H), 3.51 (t, J ¼ 6.6 Hz, 2H), 3.98 (s,
(CDCl3, 200 MHz):
d
3H), 4.22 (t, J ¼ 6 Hz, 2H), 7.16–7.23 (m, 4H), 7.37–7.53 (m, 4H), 7.73
(s, 1H), 7.96–8.02 (m, 2H), 8.70 (s, 1H); HRMS (m/z): Calculated for
C26H21N4O3SF3 (M þ H)þ ¼ 527.1364, found ¼ 527.1343.
d
55.66, 66.48, 100.49, 107.39, 108.10, 113.00, 117.64, 119.60, 119.89,
120.51, 120.85, 124.05, 125.72, 128.91, 134.50, 138.50, 139.60, 147.70,
148.00, 151.20, 152.50, 152.92, 154.75, 156.10; HRMS (m/z): Calcu-
lated for C26H21N4O2S2F3 (M þ H)þ ¼ 543.1136, found ¼ 543.1125.
4.1.5.8. 6-[3-(Benzoxazol-2-ylthio)propoxy]-7-methoxy-N-[4-(tri-
fluoromethoxy)phenyl]quinazo-lin-4-amine (25). Using 8 and 48 as
starting materials, compound 25 was obtained as off-white solid in
60% yield; m.p. 90–94 ꢀC; IR (KBr): 520, 663, 744, 929, 1068, 1141,
1270, 1342, 1434, 1512, 1585, 1627, 2935, 3070, 3224, 3300 cmꢂ1; 1H
4.1.5.3. 6-[3-(Benzothiazol-2-ylthio)propoxy]-N-(4-bromo-2-ethyl-
phenyl)-7-methoxyquinazolin-4-amine (20). Using 11 and 47 as
starting materials, compound 20 was obtained as off-white solid in
68% yield; m.p. 204–207 ꢀC; IR (KBr): 756, 999, 1064, 1176, 1238,
1330, 1427, 1473, 1500, 1581, 1620, 2962, 3058, 3300 cmꢂ1; 1H NMR
NMR (CDCl3, 200 MHz):
d
2.42 (m, 2H), 3.51 (t, J ¼ 6.6 Hz, 2H), 3.98
(s, 3H), 4.23 (t, J ¼ 6 Hz, 2H), 7.16–7.24 (m, 6H), 7.37–7.42 (m, 1H),
7.49–7.53 (m, 1H). 7.67 (s, 1H), 7.74 (d, J ¼ 9 Hz, 2H), 8.66 (s, 1H); 13C
NMR (CDCl3, 200 MHz):
d 30.88, 31.18, 58.29, 69.45, 105.32, 109.72,
(CDCl3, 200 MHz):
d
1.22 (t, J ¼ 7.4 and 7.6 Hz, 3H), 2.46 (m, 2H),
111.19, 112.51, 120.00, 120.56, 123.63, 125.84, 126.59, 126.93, 141.09,
144.10, 146.20, 149.49, 150.41, 154.10, 155.15, 156.15, 156.84, 158.53,
167.00; GC–MS (m/z): 542 (Mþ).
2.62 (q, J ¼ 7.4 and 7.6 Hz, 2H), 3.59 (t, J ¼ 6.6 Hz, 2H), 4.00 (s, 3H),
4.24 (t, J ¼ 6 Hz, 2H), 6.92 (s, 1H), 7.03 (s, 1H), 7.24–7.49 (m, 6H),
13C NMR (CDCl
7.69–7.78 (m, 2H), 8.57 (s, 1H);
3, 200 MHz): d 13.17,
23.86, 28.42, 29.67, 55.69, 66.75, 100.67, 107.59, 108.00, 120.45,
120.89, 123.91, 125.60, 127.12, 129.24, 131.29, 133.95, 134.10, 135.10,
136.00, 137.80, 138.00, 139.80, 140.00, 147.12, 152.55, 153.41, 157.12;
GC–MS (m/z): 581 (Mþ).
4.1.5.9. 6-[3-(Benzoxazol-2-ylthio)propoxy]-N-(4-bromo-2-ethylphenyl)-
7-methoxy-quinazolin-4-amine (26). Using 11 and 48 as starting
materials, compound 26 was obtained as off-white solid in 70%
yield; m.p. 187–190 ꢀC; IR (KBr): 740, 856, 1002, 1064, 1130, 1211,
1242,1388, 1427, 1500, 1581, 1620, 2927, 2962, 3058, 3300 cmꢂ1; 1H
4.1.5.4. 6-[3-(Benzothiazol-2-ylthio)propoxy]-7-methoxy-N-(4-methoxy-
phenyl)quinazoline-4-amine (21). Using 12 and 47 as starting
materials, compound 21 was obtained as pale yellow solid in 60%
yield; m.p. 123–126 ꢀC; IR (KBr): 555, 756, 825, 999, 1026, 1072,
NMR (CDCl3, 200 MHz):
d
1.22 (t, J ¼ 7.4 &7.6 Hz, 3H), 2.45 (m, 2H),
2.63 (q, J ¼ 7.4 and 7.6 Hz, 2H), 3.53 (t, J ¼ 6.6 Hz, 2H), 3.99 (s, 3H),
4.23 (t, J ¼ 6 Hz, 2H), 7.06 (br s, 2H), 7.20–7.28 (m, 3H), 7.37–7.54 (m,
5H), 8.57 (s, 1H); 13C NMR (CDCl3, 200 MHz):
d 13.18, 23.88, 28.34,
1245, 1342, 1434, 1512, 1581, 1627, 2923, 3325 cmꢂ1
;
1H NMR
28.34, 55.66, 66.67, 100.98, 107.60, 108.28, 109.35, 117.80, 119.10,
123.54, 123.86, 127.14, 129.24, 131.31, 134.77, 140.00, 141.25, 147.90,
148.11, 151.00, 153.45, 154.75, 156.78, 164.0; GC–MS (m/z): 565
(Mþ).
(CDCl3, 200 MHz):
d
2.41 (m, 2H), 3.55 (t, J ¼ 6.6 Hz, 2H), 3.82 (s,
3H), 3.98 (s, 3H), 4.21 (t, J ¼ 6.2 Hz, 2H), 6.93 (d, J ¼ 8.8 Hz, 2H),
7.10 (s, 1H), 7.21 (s, 1H), 7.29–7.39 (m, 2H), 7.50 (d, J ¼ 8.8 Hz, 2H),
7.69–7.80 (m, 2H), 8.59 (s, 1H); 13C NMR (CDCl3, 200 MHz):
d
28.32, 29.68, 54.98, 55.58, 66.46, 101.18, 107.18, 108.49, 113.76,
4.1.5.10. 6-[3-(Benzoxazol-2-ylthio)propoxy]-7-methoxy-N-(4-methoxy-
phenyl)quinazolin-4-amine (27). Using 12 and 48 as starting
materials, compound 27 was obtained as pale yellow solid in 65%
yield; m.p. 138–140 ꢀC; IR (KBr): 555, 744, 856, 925, 1033, 1068,
1134, 1238, 1431, 1508, 1577, 1620, 2923, 3060, 3250 cmꢂ1; 1H NMR
120.49, 120.83, 123.95, 124.12, 125.68, 130.95, 135.00, 146.74,
147.82, 152.80, 153.77, 154.35, 156.24, 156.68, 167.20; GC–MS (m/z):
504 (Mþ).
4.1.5.5. 6-[3-(Benzothiazol-2-ylthio)propoxy]-7-methoxy-N-(4-methyl-
phenyl)quinazolin-4-amine (22). Using 13 and 47 as starting
materials, compound 22 was obtained as pale yellow solid in 65%
yield; m.p. 104–106 ꢀC; IR (KBr): 509, 756, 856, 999, 1068, 1242,
(CDCl3, 200 MHz):
d
2.45 (m, 2H), 3.53 (t, J ¼ 6.8 Hz, 2H), 3.82 (s,
3H), 3.99 (s, 3H), 4.25 (t, J ¼ 6.2 Hz, 2H), 6.94 (d, J ¼ 9 Hz, 2H), 7.10 (s,
1H), 7.22–7.29 (m, 4H), 7.38–7.42 (m, 1H), 7.49–7.55 (m, 3H), 8.60 (s,
1H); 13C NMR (CDCl3, 200 MHz):
d 28.30, 28.35, 55.00, 55.61, 66.52,