D.B. Khadka et al. / European Journal of Medicinal Chemistry 103 (2015) 69e79
77
121.5, 119.9, 119.8, 103.6, 43.9, 12.1. MS (ESI): m/z 378.1 (M þ H)þ.
HRMS (ESI): m/z 378.1433 (M þ H)þ (calcd for C19H19F3N3O2,
378.1429).
127.8, 127.0, 125.6, 124.7, 118.5, 21.3, 20.9. HRMS (ESI): m/z 251.1187
(M þ H)þ (calcd for C16H15N2O, 251.1184).
5.1.24. 2-(3-Methoxyphenyl)-7-methylquinazolin-4(3H)-one (25)
Yield 441 mg (83%). White solid. Mp: 212e214 ꢀC. IR (cmꢁ1):
3414 (NH), 3036, 1682 (C]O). 1H NMR (500 MHz, DMSO-d6)
5.1.18. 2-(Naphthalen-1-yl)-6-(piperidin-1-yl)quinazolin-4(3H)-
one (19)
Yield 510 mg (72%). Brown solid. Mp: 231e233 ꢀC. 1H NMR
d
(ppm): 12.4 (s,1H); 8.03 (d, J ¼ 8.0 Hz, 1H), 7.77 (d, J ¼ 7.5 Hz, 1H),
(500 MHz, DMSO-d6)
d
(ppm): 12.4 (s, 1H); 8.16 (dd, J ¼ 7.5, 1.5 Hz,
7.73 (s, 1H); 7.54 (s, 1H); 7.44 (t, J ¼ 7.5 Hz, 1H), 7.32 (d, J ¼ 8.0 Hz,
1H), 8.08 (d, J ¼ 8.5 Hz, 1H), 8.02 (dd, J ¼ 7.5, 2.0 Hz, 1H), 7.74 (d,
J ¼ 7.0 Hz, 1H), 7.64e7.56 (m, 5H), 7.49 (d, J ¼ 2.0 Hz, 1H), 3.29 (t,
J ¼ 5.0 Hz, 4H), 1.66e1.65 (m, 4H), 1.59e1.58 (m, 2H). 13C NMR
1H), 7.13 (d, J ¼ 8.0 Hz, 1H), 3.85 (s, 3H), 2.46 (s, 3H). 13C NMR
(125 MHz, DMSO-d6)
d (ppm): 162.0, 159.3, 151.9, 148.7, 145.0,
134.0, 129.6, 127.9, 127.1, 125.6, 120.0, 118.5, 117.5, 112.4, 55.3, 21.2.
(125 MHz, DMSO-d6)
d
(ppm): 161.8, 150.0,146.2,138.9, 133.1, 131.8,
HRMS (ESI): m/z 267.1139 (M þ H)þ (calcd for C16H15N2O, 267.1133).
130.3, 129.9, 128.2, 127.5, 126.8, 126.2, 125.3, 125.2, 125.0, 124.0,
107.9, 49.2, 24.9, 23.7. MS (ESI): m/z 356.1 (M þ H)þ.
5.1.25. 7-Methyl-2-(3-(trifluoromethyl)phenyl)quinazolin-4(3H)-
one (26)
5.1.19. 2-(2,3-Dimethoxyphenyl)-6-(piperidin-1-yl)quinazolin-
4(3H)-one (20)
Yield 452 mg (70%). White solid. Mp: 294e296 ꢀC. IR (cmꢁ1):
3414 (NH), 3069, 1664 (C]O). 1H NMR (500 MHz, DMSO-d6)
Yield: 770 mg (67%). Brown solid. Mp: 182e184 ꢀC. 1H NMR
d
(ppm): 12.6 (s,1H), 8.53 (s, 1H), 8.47 (d, J ¼ 7.5 Hz, 1H), 8.05 (d,
(500 MHz, CDCl3)
d
(ppm): 10.91 (s, 1H); 7.96 (dd, J ¼ 8, 1.5 Hz, 1H),
J ¼ 8 Hz, 1H), 7.95 (d, J ¼ 8.0 Hz, 1H), 7.80 (t, J ¼ 8.0 Hz, 1H), 7.60 (s,
7.67 (d, J ¼ 9 Hz, 1H), 7.64 (d, J ¼ 3 Hz, 1H), 7.44 (dd, J ¼ 9, 3 Hz, 1H),
7.20 (t, J ¼ 8 Hz, 1H), 7.06 (dd, J ¼ 9, 3 Hz, 1H), 3.94 (s, 3H), 3.92 (s,
3H), 3.32 (q, J ¼ 5.5 Hz, 4H), 1.75e1.71 (m, 4H), 1.65e1.61 (m, 2H).
1H); 7.37 (d, J ¼ 8.0 Hz, 1H), 3.85 (s, 3H), 2.51 (s, 3H). 13C NMR
(125 MHz, DMSO-d6) d (ppm): 161.9, 150.9, 148.5, 145.1, 133.7, 131.6,
129.7 (2JCeF ¼ 31.8 Hz), 129.4, 128.3, 127.4, 127.2, 125.6, 124.4
(3JCeF ¼ 3.8 Hz),123.9 (1JCeF ¼ 271.1 Hz),118.7, 21.2. HRMS (ESI): m/z
305.0908 (M þ H)þ (calcd for C16H12F3N2O, 305.0901).
13C NMR (125 MHz, CDCl3)
d (ppm): 161.8, 152.9, 147.7, 147.3, 128.7,
125.4, 124.8, 124.4, 122.1, 121.9, 114.9, 109.3, 61.6, 56.1, 50.1, 25.5,
24.2. MS (ESI): m/z 366.1 (M þ H)þ. HRMS (ESI): m/z 366.1821
(M þ H)þ (calcd for C21H24N3O3, 366.1817).
5.1.26. 7-Methyl-2-(2-(trifluoromethoxy)phenyl)quinazolin-4(3H)-
one (27)
5.1.20. 6-Morpholino-2-(naphthalen-1-yl)quinazolin-4(3H)-one
(21)
Yield 441 mg (69%). Light yellow solid. Mp: 204e205 ꢀC. IR
(cmꢁ1): 3420 (NH), 3022, 1676 (C]O). 1H NMR (500 MHz, CDCl3)
Yield 564 mg (79%). Yellow solid. Mp: 291e293 ꢀC. 1H NMR
d
(ppm): 10.3 (s, 1H); 8.17 (d, J ¼ 8.0 Hz, 1H), 8.10 (dd, J ¼ 8.0, 1.0 Hz,
(500 MHz, DMSO-d6)
d
(ppm): 12.4 (s, 1H); 8.17 (dd, J ¼ 7.0, 2.0 Hz,
1H), 7.61e7.58 (m, 2H); 7.49 (t, J ¼ 7.5 Hz, 1H), 7.40 (d, J ¼ 8.0 Hz,
1H), 8.09 (d, J ¼ 8.0 Hz, 1H), 8.02 (dd, J ¼ 7.5, 2.0 Hz, 1H), 7.76 (d,
J ¼ 7.0 Hz, 1H), 7.64e7.56 (m, 5H), 7.52 (d, J ¼ 2.5 Hz, 1H), 3.79 (t,
J ¼ 5.0 Hz, 4H), 3.25 (t, J ¼ 5.0 Hz, 4H). 13C NMR (125 MHz, DMSO-
1H), 7.34 (d, J ¼ 8.0 Hz, 1H), 2.52 (s, 3H). 13C NMR (125 MHz, CDCl3)
d
(ppm): 161.9, 149.2, 149.0, 146.4, 145.9, 132.5, 131.8, 128.9, 127.8,
127.6, 126.7, 126.3, 121.4, 120.1 (1JCeF ¼ 256 Hz), 118.6, 21.9. HRMS
d6)
d (ppm): 161.8, 150.5, 149.7, 141.8, 133.1, 131.8, 130.3, 130.0,
(ESI): m/z 321.0844 (M þ H)þ (calcd for C16H12F3N2O2, 321.0850).
128.3,128.2,127.5, 126.9, 126.2, 125.3, 125.0,123.4, 121.7, 107.8, 65.9,
48.2. MS (ESI): m/z 358.1 (M þ H)þ.
5.1.27. 7-Methyl-2-(3-(trifluoromethoxy)phenyl)quinazolin-4(3H)-
one (28)
5.1.21. 7-Methyl-2-(naphthalen-1-yl)quinazolin-4(3H)-one (22)
Yield 399 mg (70%). Light-yellow solid. Mp: 293e294 ꢀC. IR
(cmꢁ1): 3421 (NH), 3041, 1659 (C]O). 1H NMR (500 MHz, DMSO-
Yield 454 mg (71%). Light yellow solid. Mp: 250e252 ꢀC. IR
(cmꢁ1): 3420 (NH), 3022, 1676 (C]O). 1H NMR (500 MHz, CDCl3)
d
(ppm): 12.5 (s, 1H); 8.30 (s, 1H); 8.29 (d, J ¼ 8.0 Hz, 1H), 8.19 (d,
d6)
d
(ppm): 12.5 (s, 1H); 8.17 (d, J ¼ 8.0 Hz, 1H), 8.12e8.09 (m, 2H),
J ¼ 8.0 Hz,1H), 7.61 (s,1H); 7.58 (d, J ¼ 8.0 Hz,1H), 7.42 (d, J ¼ 8.0 Hz,
8.04 (d, J ¼ 7.5 Hz, 1H), 7.78 (d, J ¼ 7.0 Hz, 1H), 7.66e7.54 (m, 4H),
1H), 7.33 (d, J ¼ 8.0 Hz, 1H), 2.53 (s, 3H). 13C NMR (125 MHz, CDCl3)
7.40 (d, J ¼ 7.5 Hz, 1H), 2.49 (s, 3H). 13C NMR (125 MHz, DMSO-d6)
d
(ppm): 162.2, 150.2, 149.7, 149.4, 146.1, 134.9, 130.2, 128.7, 127.8,
d
(ppm): 161.7, 153.6, 148.8, 144.9, 133.1, 131.6, 130.3, 130.2, 128.2,
126.1, 125.9, 123.6, 120.6, 120.5 (1JCeF ¼ 256 Hz), 118.4, 21.9. HRMS
128.1, 127.6, 127.0, 126.9, 126.3, 125.6, 125.1, 125.0, 118.7, 21.3. HRMS
(ESI): m/z 321.0856 (M þ H)þ (calcd for C16H12F3N2O2, 321.0850).
(ESI): m/z 287.1188 (M þ H)þ (calcd for C20H17NO, 287.1184).
5.1.28. 2-(2-Fluorophenyl)-7-methylquinazolin-4(3H)-one (29)
Yield 356 mg (55%). White solid. Mp: 185e187 ꢀC. IR (cmꢁ1):
3420 (NH), 3024, 1680 (C]O). 1H NMR (500 MHz, DMSO-d6)
5.1.22. 7-Methyl-2-(o-tolyl)quinazolin-4(3H)-one (23)
Yield 290 mg (58%). White solid. Mp: 219e221 ꢀC. IR (cmꢁ1):
3420 (NH), 3041, 1682 (C]O). 1H NMR (500 MHz, DMSO-d6)
d
(ppm): 12.4 (s, 1H), 8.05 (d, J ¼ 8.0 Hz, 1H), 7.78 (td, J ¼ 7.5, 1.5 Hz,
d
(ppm): 12.3 (s,1H), 8.04 (d, J ¼ 8.0 Hz,1H), 7.49e7.48 (m, 2H); 7.42
1H), 7.65e7.60 (m, 1H), 7.54 (s, 1H), 7.41e7.36 (m, 3H), 2.48 (s, 3H).
(t, J ¼ 7.5 Hz, 1H), 7.36e7.30 (m, 3H), 2.46 (s, 3H), 2.37 (s, 3H). 13
C
13C NMR (125 MHz, DMSO-d6)
d
(ppm): 161.3, 159.5
NMR (125 MHz, DMSO-d6)
d
(ppm): 161.6, 154.3, 148.8, 144.8, 136.0,
(1JCeF ¼ 248 Hz), 149.9, 148.7, 145.1, 132.8 (3JCeF ¼ 8.5 Hz), 130.9,
128.4,127.1,125.6,124.6 (4JCeF ¼ 3.3 Hz),122.3 (3JCeF ¼ 13 Hz),118.6,
116.1 (2JCeF ¼ 21.2 Hz), 21.9. HRMS (ESI): m/z 255.0929 (M þ H)þ
(calcd for C15H12FN2O, 255.0933).
134.2, 130.4, 129.7, 129.0, 127.9, 126.9, 125.64, 125.61, 118.5, 21.3,
19.5. HRMS (ESI): m/z 251.1189 (M þ H)þ (calcd for C16H15N2O,
251.1184).
5.1.23. 7-Methyl-2-(m-tolyl)quinazolin-4(3H)-one (24)
5.1.29. 2-(3-Fluorophenyl)-7-methylquinazolin-4(3H)-one (30)
Yield 360 mg (71%). White solid. Mp: 291e293 ꢀC. IR (cmꢁ1):
3420 (NH), 3024, 1680 (C]O). 1H NMR (500 MHz, DMSO-d6)
Yield 398 mg (80%). White solid. Mp: 241e243 ꢀC. IR (cmꢁ1):
3414 (NH), 3036, 1682 (C]O). 1H NMR (500 MHz, DMSO-d6)
d
(ppm): 12.3 (s, 1H), 8.02 (d, J ¼ 8.5 Hz, 1H), 8.01 (s, 1H), 7.96 (d,
d
(ppm): 12.5 (s, 1H), 8.05 (d, J ¼ 8.0 Hz, 2H), 7.99 (d, J ¼ 8.5 Hz, 1H),
J ¼ 7.5 Hz, 1H), 7.54 (s, 1H); 7.43e7.38 (m, 2H), 7.33 (d, J ¼ 8.0 Hz,
7.62e7.57 (m, 2H), 7.78 (td, J ¼ 7.5, 2.5 Hz, 1H), 7.37 (d, J ¼ 7.5 Hz,
1H), 2.46 (s, 3H), 2.40 (s, 3H). 13C NMR (125 MHz, DMSO-d6)
1H), 2.51 (s, 3H). 13C NMR (125 MHz, DMSO-d6)
d (ppm): 162.0
d
(ppm): 162.0, 152.3, 148.8, 144.9, 137.8, 132.6, 131.8, 128.4, 128.1,
(1JCeF ¼ 242.3 Hz), 161.9, 151.0, 148.5, 145.1, 135.0 (3JCeF ¼ 8.5 Hz),