JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
557
1
H NMR (CDCl
3
, 400 MHz), d 8.38 (s, 1H), 8.30 (dd, J¼ 8.0, 0.9 Hz, 1H), 4.7 Hz, 2H),7.51 (dd, J ¼ 10.9, 4.1 Hz, 1H), 7.35–7.28 (m, 1H), 7.16 (d,
7
.87 (d, J ¼ 8.7 Hz, 2H), 7.75 (ddd, J ¼ 18.1, 12.5, 4.4 Hz, 2H), 7.55–7.47 J ¼ 8.7 Hz, 2H), 6.93 (ddd, J ¼ 18.7, 12.0,4.7 Hz, 3H), 5.25 (s, 2H),
1
3
(
m, 1H), 7.38 (t, J¼ 7.8 Hz, 2H), 7.24–7.11 (m, 5H), 5.24 (s, 2H), 3.74 (s, 3.75 (s, 3H);
3
C NMR (CDCl , 100 MHz), d 164.5, 162.3, 160.3,
13
3
1
1
H); C NMR (CDCl , 100 MHz), d 162.3, 160.1, 159.3, 152,1, 151.2, 160.1, 153.9, 151.1, 146.7, 134.4, 130.9, 130.1, 127.7, 127.5, 126.9,
3
46.7, 134.4, 130.7, 130.5, 129.2, 127.7, 126.9, 125.8, 121.0, 120.9, 121.0, 116.8, 115.2, 112.5, 112.3, 108.2, 107.9, 70.1, 30.9; HRMS
15.1, 70.1, 30.9; HRMS (calcd.), m/z[M þ H] , 370.1540(370.1550).
þ
þ
(calcd.), m/z[M þ H] , 388.1446(388.1456).
2
.1.4.2. (E)-3-methyl-2-((4-((o-tolylimino)methyl)phenoxy)methyl)- 2.1.4.8. (E)-2-((4-(((4-fluorophenyl)imino)methyl)phenoxy)methyl)-3-
quinazolin-4(3H)-one (5 b). White solid; yield 73%; m.p. methylquinazolin-4(3H)-one (5 h). White solid; yield 75%; m.p.
ꢂ
1
ꢂ
1
1
62–164 C; H NMR (CDCl , 400 MHz), d 8.33–8.26 (m, 2H), 7.88 (d, 200–202 C; H NMR (CDCl , 400 MHz), d 8.36 (s, 1H), 8.30 (d,
3
3
J ¼ 8.7 Hz, 2H), 7.75 (ddd, J ¼ 21.8, 11.5, 4.2 Hz, 2H), 7.56–7.48 (m, J ¼ 8.0 Hz, 1H), 7.86 (d, J ¼ 8.5 Hz, 2H), 7.75 (dt, J ¼ 19.0, 7.6 Hz,
1
5
1
1
3
H), 7.15 (ddt, J ¼ 21.5, 13.8,7.3 Hz, 5H), 6.90 (d, J ¼ 7.7 Hz, 1H), 2H),7.52 (t, J ¼ 7.5 Hz, 1H), 7.20–7.11 (m, 4H), 7.06 (t, J ¼ 8.5 Hz,
1
3
1
3
.24 (s, 2H), 3.75 (s, 3H), 2.34 (s, 3H); C NMR (CDCl , 100 MHz), d 2H), 5.25 (s, 2H), 3.75 (s, 3H); C NMR (CDCl , 100 MHz), d 162.3,
3
3
62.3, 160.0, 158.3, 151.2, 151.1, 146.7, 134.4, 131.9, 130.8, 130.5, 160.1, 159.9, 159.1, 151.2, 148.1, 146.7, 134.4, 130.6, 130.4, 127.7,
30.3, 127.7, 127.5, 126.9, 126.7, 125.5, 121.0, 117.7, 115.1, 70.1, 127.5, 126.9, 122.3, 122.2, 121.0, 116.0, 115.8, 115.1, 70.1, 30.9;
þ
þ
0.9, 17.9; HRMS (calcd.), m/z[M þ H] , 384.1698(384.1707).
HRMS (calcd.), m/z[M þ H] , 388.1448(388.1456).
2
.1.4.3. (E)-3-methyl-2-((4-((p-tolylimino)methyl)phenoxy)methyl)- 2.1.4.9. (E)-2-((4-(((3-chlorophenyl)imino)methyl)phenoxy)methyl)-
ꢂ
quinazolin-4(3H)-one (5c). White solid; yield 84%; m.p. 182–184 C; 3-methylquinazolin-4(3H)-one (5i). White solid; yield 80%; m.p.
1
ꢂ
1
H NMR (CDCl , 400 MHz), d 8.39 (s, 1H), 8.29 (d, J ¼ 7.9 Hz, 1H), 179–181 C; H NMR (CDCl , 400 MHz), d 8.34 (s, 1H), 8.33–8.26 (m,
3
3
7
1
3
1
1
3
.85 (d, J ¼ 8.7 Hz, 2H), 7.79–7.67 (m, 2H), 7.50 (dd, J ¼ 8.6, 4.0 Hz, 1H), 7.86 (d, J ¼ 8.7 Hz, 2H), 7.79–7.69 (m, 2H), 7.55–7.48 (m, 1H),
H), 7.14 (dt, J ¼ 12.4, 8.2 Hz, 6H), 5.23 (s, 2H), 3.74 (s, 3H), 2.35 (s, 7.29 (t, J ¼ 7.9 Hz, 1H), 7.17 (t, J ¼ 8.4 Hz, 4H), 7.06 (d, J ¼ 8.2 Hz,
1
3
13
H); C NMR (CDCl , 100 MHz), d 162.3, 160.0, 158.4, 151.2, 149.5, 1H), 5.25 (s, 2H), 3.75 (s, 3H); C NMR (CDCl , 100 MHz), d 162.3,
3
3
46.7, 135.6, 134.3, 130.7, 130.5, 129.8, 127.7, 127.5, 126.9, 121.0, 160.4, 160.2, 153.4, 151.1, 146.7, 134.7, 134.4, 130.9, 130.2, 127.7,
þ
20.8, 115.1, 70.1, 30.8, 21.0; HRMS (calcd.), m/z[M þ H] , 127.5, 126.9, 125.7, 121.0, 120.9, 119.5, 115.2, 70.1, 30.9; HRMS
þ
84.1697(384.1707).
.1.4.4.
(calcd.), m/z[M þ H] , 404.1150(404.1160).
2
(E)-2-((4-(((2-methoxyphenyl)imino)methyl)phenoxy)- 2.1.4.10. (E)-2-((4-(((3-bromophenyl)imino)methyl)phenoxy)methyl)-
methyl)-3-methylquinazolin-4(3H)-one (5d). White solid; yield 81%; 3-methylquinazolin-4(3H)-one (5j). White solid; yield 85%; m.p.
ꢂ
1
ꢂ
1
m.p. 141–143 C; H NMR (CDCl
J ¼ 8.0, 0.7 Hz, 1H), 7.89 (d, J ¼ 8.7 Hz, 2H), 7.79–7.67 (m, 2H), J ¼ 7.9 Hz, 1H), 7.86 (d, J ¼ 8.6 Hz, 2H), 7.80–7.68 (m, 2H), 7.52 (t,
3
, 400 MHz), d 8.39 (s, 1H), 8.30 (dd, 176–178 C; H NMR (CDCl , 400 MHz), d 8.34 (s, 1H), 8.30 (d,
3
7
.56–7.47 (m, 1H), 7.17 (ddd, J ¼ 18.8, 10.0, 5.6 Hz, 3H), 7.01–6.91 J ¼ 7.2 Hz, 1H), 7.33 (d, J ¼ 6.6 Hz, 2H), 7.24 (t, J ¼ 8.1 Hz, 1H), 7.14
13 13
(
m, 3H), 5.24 (s, 2H), 3.87 (s, 3H), 3.74 (s, 3H); C NMR (CDCl
3
,
(dd, J ¼ 19.3, 8.2 Hz, 3H), 5.26 (s, 2H), 3.75 (s, 3H); C NMR (CDCl
3
,
1
1
7
00 MHz), d 162.3, 160.2, 152.3, 151.2, 146.7, 141.9, 134.4, 130.8, 100 MHz), d 162.3, 160.4, 160.2, 153.6, 151.1, 146.7, 134.4, 130.9,
30.7, 127.7, 127.5, 126.9, 126.5, 121.1, 121.0, 120.2, 115.0, 111.5, 130.4, 130.1, 128.6, 127.7, 127.5, 126.9, 123.7, 122.8, 121.0, 120.0,
0.0, 55.9, 30.9; HRMS (calcd.), m/z[M þ H] , 400.1645(400.1656).
þ
þ
115.2, 70.1, 30.9; HRMS (calcd.), m/z[M þ H] , 448.0647(448.0655).
2
.1.4.5.
(E)-2-((4-(((4-methoxyphenyl)imino)methyl)phenoxy)- 2.1.4.11.
(E)-2-((4-(((3,4-difluorophenyl)imino)methyl)phenoxy)-
methyl)-3-methylquinazolin-4(3H)-one (5e). White solid; yield 88%; methyl)-3-methylquinazolin-4(3H)-one (5k). White solid; yield 80%;
ꢂ
1
ꢂ
1
m.p. 180–182 C; H NMR (CDCl , 400 MHz), d 8.40 (s, 1H), 8.29 (dd, m.p. 152–154 C; H NMR (CDCl , 400 MHz), d 8.34 (s, 1H),
3
3
J ¼ 8.0, 1.0 Hz, 1H), 7.85 (d, J ¼ 8.8 Hz, 2H), 7.80–7.65 (m, 2H), 8.32–8.26 (m, 1H), 7.86 (d, J ¼ 8.8 Hz, 2H), 7.76 (ddd, J ¼ 20.4, 13.6,
7
6
.55–7.46 (m, 1H), 7.25–7.16 (m, 2H), 7.13 (d, J ¼ 8.8 Hz, 2H), 4.4 Hz, 2H), 7.56–7.49 (m, 1H), 7.20–7.10 (m, 3H), 7.03 (ddd,
13
.97–6.85 (m, 2H), 5.23 (s, 2H), 3.81 (s, 3H), 3.74 (s, 3H); C NMR J ¼ 11.4, 7.2, 2.5 Hz, 1H), 6.96–6.89 (m, 1H), 5.26 (s, 2H), 3.76 (s,
1
3
(CDCl , 100 MHz), d 162.3, 159.82, 158.1, 157.3, 151.2, 146.7, 145.0, 3H); C NMR (CDCl , 100 MHz), d 162.3, 160.4, 159.9, 151.1, 146.7,
3
3
1
7
34.4, 130.8, 130.4, 127.7, 127.5, 126.9, 122.1, 121.0, 115.1, 114.4, 134.4, 130.8, 130.0, 127.7, 127.5, 126.9, 121.0, 117.5, 117.3, 117.0,
þ
0.1, 55.5, 30.9; HRMS (calcd.), m/z[M þ H] , 400.1645(400.1656).
116.9, 116.8, 115.2, 110.0, 109.8, 70.1, 30.9; HRMS (calcd.), m/
z[M þ H] , 406.1354(406.1362).
þ
2
.1.4.6. (E)-2-((4-(((2-fluorophenyl)imino)methyl)phenoxy)methyl)-3-
methylquinazolin-4 (3H)-one (5f). White solid; yield 76%; m.p. 2.1.4.12.
(E)-2-((4-(((3,5-difluorophenyl)imino)methyl)phenoxy)-
ꢂ
1
1
43–145 C; H NMR (CDCl , 400 MHz), d 8.44 (s, 1H), 8.30 (dd, methyl)-3-methylquinazolin-4(3H)-one (5 l). White solid; yield 87%;
3
ꢂ
1
J ¼ 8.0, 0.8 Hz, 1H), 7.89 (d, J ¼ 8.8 Hz, 2H), 7.80–7.69 (m, 2H), m.p. 220–221 C; H NMR (DMSO-d , 400 MHz), d 8.58 (s, 1H), 8.17
6
1
3
7
.56–7.48 (m, 1H), 7.18–7.09 (m, 6H), 5.25 (s, 2H), 3.75 (s, 3H);
C
(dd, J ¼ 8.0, 1.1 Hz, 1H), 7.91 (d, J ¼ 8.9 Hz, 2H), 7.83 (dd, J ¼ 11.1,
NMR (CDCl
3
, 100 MHz), d 162.3, 161.8, 160.4, 156,5, 154.0, 151.1, 4.2 Hz, 1H), 7.65 (d, J ¼ 7.7 Hz, 1H),7.60–7.53 (m, 1H), 7.27 (d,
1
1
3
46.7, 140.0, 134.4, 130.9, 130.3, 127.7, 127.5, 126.9, 124.5, 122.0, J ¼ 8.8 Hz, 2H), 7.09 (td, J ¼ 9.4, 4.7 Hz, 1H), 7.03–6.96 (m, 2H), 5.42
þ 13
21.0, 116.3, 116.1, 115.1, 70.1, 30.9; HRMS (calcd.), m/z[M þ H] , (s, 2H), 3.62 (s, 3H); C NMR (DMSO-d
6
, 100 MHz), d 162.0, 161.7,
88.1445(388.1456).
160.8, 160.3, 159.6, 152.7, 148.5, 146.9, 134.9, 130.9, 130.1, 127.8,
1
27.6, 126.7, 123.2, 123.1, 120.8, 116.4, 116.2, 115.8, 69.0, 30.4;
þ
HRMS (calcd.), m/z[M þ H] , 406.1355(406.1362).
2
.1.4.7. (E)-2-((4-(((3-fluorophenyl)imino)methyl)phenoxy)methyl)-3-
methylquinazolin-4(3H)-one (5 g). White solid; yield 72%; m.p.
ꢂ
1
1
68–170 C; H NMR (CDCl
3
, 400 MHz), d 8.35 (s, 1H), 8.30 (d, 2.1.4.13.
(E)-2-((4-(((2,6-difluorophenyl)imino)methyl)phenoxy)-
J ¼ 7.9 Hz, 1H), 7.86 (d, J ¼ 8.7 Hz, 2H), 7.75 (ddd, J ¼ 19.2, 13.1, methyl)-3-methylquinazolin-4(3H)-one (5 m). White solid; yield