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HRMS (ESI+): m/z calcd for C18H16FN2O [M+H]+ 295.1241, found
295.1252.
2-Methyl-4-(1-(4-(methylthio)phenyl)vinyl)quinazoline 4i: 43%
yield, yellow oil, TLC: Rf =0.4 (cyclohexane/EtOAc 7:3); IR (neat):
;
n˜ =1751, 1554, 1492, 1326, 1215 cmÀ1 1H NMR (300 MHz, CDCl3):
2-Methoxy-5-(1-(2-methylquinazolin-4-yl)vinyl)aniline 4d: Com-
pound 4d was prepared by coupling N-toluenesulfonylhydrazone
7e with 5a (see general procedure) followed by removal of the
NHAc protecting group. The resulting crude mixture after coupling
7e with 5a was dissolved in MeOH (1 mL), and KOH (20 mmol)
was added. The mixture was heated and stirred in sealed tube at
1008C for 12 h. The resulting suspension was filtered and purified
by silica gel chromatography to furnish compound 4d as a yellow
oil, 27% yield, TLC: Rf =0.1 (cyclohexane/EtOAc 7:3); IR (neat): n˜ =
d=7.96 (d, 1H, J=8.4 Hz), 7.83–7.76 (m, 2H), 7.42–7.36 (m, 1H),
7.20 (d, 2H, J=8.6 Hz), 7.14 (d, 2H, J=8.7 Hz), 6.09 (s, 1H), 5.52 (s,
1H), 2.91 (s, 3H), 2.42 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=
169.4, 164.1, 151.1, 145.0, 139.2, 135.4, 133.9, 128.1, 127.0 (2C),
126.9, 126.8, 126.3 (2C), 121.6, 118.1, 26.7, 15.5 ppm; MS (APCI+):
m/z 293 [M+H]+; HRMS (ESI+): m/z calcd for C18H17N2S [M+H]+
293.1107, found 293.1119.
2-Methyl-4-(1-(naphthalen-2-yl)vinyl)quinazoline 4j: 36% yield,
white solid, mp: 113.68C; TLC: Rf =0.2 (cyclohexane/EtOAc 7:3); IR
1614, 1567, 1553, 1441, 1330, 1219 cmÀ1 1H NMR (300 MHz,
;
(neat): n˜ =1614, 1568, 1490, 1325, 1168, 906 cmÀ1
;
1H NMR
CD3COCD3): d=7.94–7.84 (m, 3H), 7.52–7.46 (m, 1H), 6.76 À6.72
(m, 2H), 6.54 (dd, 1H, J=8.3 Hz, J=2.3 Hz), 5.96 (s, 1H), 5.33 (s,
1H), 4.41 (brs, 2H), 3.81 (s, 3H), 2.79 ppm (s, 3H); 13C NMR
(75 MHz, CD3COCD3): d=170.7, 164.6, 152.1, 148.2, 147.1, 138.5,
134.4, 133.1, 128.9, 127.8, 127.3, 122.9, 116.6, 116.1, 113.0, 111.0,
55.8, 26.6 ppm; MS (APCI+): m/z 292 [M+H]+; HRMS (ESI+): m/z
calcd for C18H18N3O [M+H]+ 292.1444, found 292.1457.
(300 MHz, CDCl3): d=8.01 (d, 1H, J=8.4 Hz), 7.86 (d, 1H, J=
8.4 Hz), 7.83–7.77 (m, 3H), 7.68–7.65 (m, 1H), 7.60–7.57 (m, 2H),
7.46–7.34 (m, 3H), 6.28 (s, 1H), 5.68 (s, 1H), 2.98 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): d=169.6, 164.1, 151.1, 145.6, 136.1,
134.0, 133.3, 133.1, 128.5, 128.4, 128.0, 127.6, 127.0, 126.8, 126.5,
126.4, 126.4, 124.1, 121.7, 119.3, 26.8 ppm; MS (ESI+): m/z 297 [M+
H]+; HRMS (ESI+): m/z calcd for C21H17N2 [M+H]+ 297.1386, found
297.1393.
4-[1-(3,4-Dimethoxyphenyl)vinyl]-2-methylquinazoline 4e: 48%
yield, yellow oil, TLC: Rf =0.1 (cyclohexane/EtOAc 7:3); IR (neat):
;
n˜ =1554, 1514, 1464, 1326, 1221, 1143 cmÀ1 1H NMR (300 MHz,
CDCl3): d=7.96 (d, 1H, J=8.4 Hz), 7.87–7.78 (m, 2H), 7.41 (t, 1H,
J=7.6 Hz), 6.97 (d, 1H, J=1.6 Hz), 6.76–6.68 (m, 2H), 6.03 (s, 1H),
5.48 (s, 1H), 3.84 (s, 3H), 3.41 (s, 3H), 2.93 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=169.7, 164.1, 151.1, 149.5, 149.1, 145.3, 133.9,
131.8, 128.1, 127.0, 126.7, 121.7, 120.1, 117.4, 111.1, 109.5, 56.0 (2C),
26.8 ppm; MS (APCI+): m/z 307 [M+H]+; HRMS (ESI+): m/z calcd
for C19H19N2O2 [M+H]+ 307.1441, found 307.1452.
2-Methyl-4-(1-(1-methyl-1H-indol-5-yl)vinyl)quinazoline 4k: 46%
yield, red oil, TLC: Rf =0.2 (cyclohexane/EtOAc 7:3); IR (neat): n˜ =
1
1612, 1565, 1490, 1332, 1246 cmÀ1; H NMR (300 MHz, CDCl3): d=
8.00 (d, 1H, J=8.4 Hz), 7.91 (dd, 1H, J=8.4 Hz, J=0.7 Hz), 7.83–
7.77 (ddd, 1H, J=8.4 Hz, J=6.9 Hz, J=1.4 Hz), 7.50–7.49 (m, 1H),
7.40–7.34 (ddd, 1H, J=8.4 Hz, J=6.7 Hz, J=1.3 Hz), 7.30–7.27 (m,
2H), 7.03 (d, 1H, J=3.1 Hz), 6.41 (d, 1H, J=3.1 Hz), 6.12 (d, 1H, J=
0.7 Hz), 5.53 (d, 1H, J=0.7 Hz), 3.77 (s, 3H), 2.99 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): d=170.6, 164.1, 151.0, 146.8, 136.7,
133.7, 130.7, 129.7, 128.6, 127.9, 127.4, 126.6, 121.9, 120.6, 119.7,
116.7, 109.5, 101.7, 33.0, 26.8 ppm; MS (APCI+): m/z 300 [M+H]+;
HRMS (ESI+): m/z calcd for C20H18N3 [M+H]+ 300.1495, found
300.1500.
4-[1-(3,5-Dimethoxyphenyl)vinyl]-2-methylquinazoline 4 f: 36%
yield, white solid; mp: 89.1–91.28C; TLC: Rf =0.3 (cyclohexane/
EtOAc 7:3); IR (neat): n˜ =1592, 1460, 1424, 1294, 1206, 1161 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=7.96 (d, 1H, J=8.4 Hz), 7.87–7.78 (m,
2H), 7.42 (td, 1H, J=8.1 Hz, J=1.0 Hz), 6.45 (d, 2H, J=2.1 Hz), 6.41
(d, 1H, J=2.0 Hz), 6.12 (s, 1H), 5.58 (s, 1H), 3.72 (s, 6H), 2.93 ppm
(s, 3H); 13C NMR (75 MHz, CDCl3): d=169.3, 164.1, 161.0 (2C), 151.1,
145.7, 141.0, 134.0, 128.1, 127.0, 126.8, 121.7, 119.5, 105.4 (2C),
100.2, 55.5 (2C), 26.8 ppm; MS (APCI+): m/z 307 [M+H]+; HRMS
(ESI+): m/z calcd for C19H19N2O2 [M+H]+ 307.1441, found 307.1446.
2-Chloro-4-[1-(4-methoxyphenyl)vinyl]quinazoline 4l: 46% yield,
yellow–brown oil, TLC: Rf =0.4 (cyclohexane/EtOAc 7:3); IR (neat):
;
n˜ =1673, 1597, 1511, 1246, 1175 cmÀ1 1H NMR (300 MHz, CDCl3):
d=8.0 (dd, 1H, J=8.5 Hz, J=1.1 Hz), 7.90–7.85 (m, 2H), 7.49 (td,
1H, J=8.5 Hz, J=1.1 Hz), 7.23 (d, 2H, J=8.8 Hz), 6.84 (d, 2H, J=
8.8 Hz), 6.06 (s, 1H), 5.55 (s, 1H), 3.79 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=173.1, 160.1, 157.3, 152.7, 144.2, 135.1, 131.1,
128.1 (2C), 128.1, 127.9, 127.5, 122.4, 118.6, 114.3 (2C), 55.4 ppm;
MS (APCI+): m/z 297 [M+H]+.
2-Methyl-4-[1-(3,4,5-trimethoxyphenyl)vinyl]quinazoline
4g:
40% yield, yellow solid; mp: 127–1288C; TLC: Rf =0.2 (cyclohex-
ane/EtOAc 7:3); IR (neat): n˜ =1553, 1506, 1464, 1410, 1331, 1242,
;
1128 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.97 (d, 1H, J=8.5 Hz),
7.90–7.80 (m, 2H), 7.45 (td, 1H, J=8.2 Hz, J=1.1 Hz), 6.54 (s, 2H),
6.07 (s, 1H), 5.56 (s, 1H), 3.84 (s, 3H), 3.72 (s, 6H), 2.94 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): d=169.3, 164.1, 153.4 (2C), 151.2, 145.7,
138.6, 134.7, 134.0, 128.1, 127.0, 126.9, 121.7, 119.0, 104.5 (2C),
61.0, 56.3 (2C), 26.8 ppm; MS (ESI+): m/z 359 [M+Na]+; HRMS
(ESI+): m/z calcd for C20H21N2O3 [M+H]+ 337.1547, found 337.1547.
2-Chloro-4-[1-(3,4-dimethoxyphenyl)vinyl]quinazoline 4m: 19%
yield, yellow oil, TLC: Rf =0.3 (cyclohexane/EtOAc 7:3); IR (neat):
n˜ =1665, 1595, 1563, 1514, 1465, 1264, 1143 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=8.00 (d, 1H, J=8.9 Hz), 7.91–7.85 (m, 2H),
7.49 (td, 1H, J=8.2 Hz, J=1.2 Hz), 6.95 (d, 1H, J=2.0 Hz), 6.77 (d,
1H, J=8.4 Hz), 6.71 (dd, 1H, J=8.3 Hz, J=2.0 Hz), 6.05 (s, 1H), 5.59
(s, 1H), 3.86 (s, 3H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=
172.8, 157.2, 152.7, 149.7, 149.2, 144.5, 135.2, 131.5, 128.0, 128.0,
127.4, 122.4, 120.2, 119.2, 111.2, 109.6, 56.1, 56.0 ppm; MS (APCI+):
m/z 327 [M+H]+; HRMS (ESI+): m/z calcd for C18H16ClN2O2 [M+H]+
327.0895, found 327.0904.
2-Methyl-4-(1-(4-(trifluoromethoxy)phenyl)vinyl)quinazoline 4h:
78%, yellow oil, TLC: Rf =0.3 (cyclohexane/EtOAc 7:3); IR (neat):
;
n˜ =1554, 1509, 1490, 1254, 1207, 1164 cmÀ1 1H NMR (300 MHz,
CDCl3): d=8.00 (d, 1H, J=8.2 Hz), 7.85–7.82 (m, 2H), 7.49–7.43 (td,
1H, J=7.4 Hz, J=1.1 Hz), 7.36 (d, 2H, J=8.9 Hz), 7.15 (d, 2H, J=
8.1 Hz), 6.16 (s, 1H), 5.62 (s, 1H), 2.93 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=169.2, 164.1, 151.1, 149.3, 144.3, 137.4, 134.3, 128.3 (2C),
128.2, 127.1, 126.7, 121.6, 121.1 (2C), 120.4 (q, J=256.5 Hz), 119.9,
26.8 ppm. 19F NMR (188 MHz, CDCl3): d=À58.23; MS (APCI+): m/z
331 [M+H]+; HRMS (ESI+): m/z calcd for C18H14F3N2O [M+H]+
331.1053, found 331.1064.
2-Chloro-4-[1-(3,4,5-trimethoxyphenyl)vinyl]quinazoline
4n:
34% yield, white solid; mp: 135.1–1368C; TLC: Rf =0.4 (cyclohex-
ane/EtOAc 7:3); IR (neat): n˜ =1580, 1528, 1401, 1316, 1277, 1243,
;
1121 cmÀ1 1H NMR (300 MHz, CDCl3): d=8.01 (d, 1H, J=8.9 Hz),
7.92–7.87 (m, 2H), 7.55–7.49 (m, 1H), 6.52 (s, 2H), 6.09 (s, 1H), 5.66
(s, 1H), 3.85 (s, 3H), 3.66 ppm (s, 6H); 13C NMR (75 MHz, CDCl3): d=
172.4, 157.2, 153.5 (2C), 152.7, 144.9, 138.8, 135.3, 134.3, 128.1 (2C),
ChemMedChem 2015, 10, 1392 – 1402
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