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C. Jiang et al. / Bioorg. Med. Chem. 19 (2011) 5612–5627
8.1.65. N-Methyl-2-amino-5-(pyrrolidin-1-yl)benzamide (14c)
Following the synthetic procedure of compound (14a), the title
compound was obtained from compound (13c) (0.50 g, 2.00
mmol) as a pale yellow powder (0.40 g, 91.32%): mp149–152 °C;
IR (cmꢀ1): 3476, 3419, 2955, 2833, 1641, 1583, 1504, 1484,
1371, 1166, 810, 612; 1H NMR (CDCl3): d 1.98 (m, 4H), 2.97 (d,
J = 5.10, 3H), 3.24 (m, 4H), 6.30 (br, 1H), 6.56–6.69 (m, 3H); EI-
MS: 219 [M].
8.1.71. 2-Phenyl-3-methyl-6-(morphilin-4-yl)-1,2,3,4-
tetrahydro-1H-quinazolin-4-one (15c)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14b) (0.35 g,
1.49 mmol), benzaldehyde (0.32 g, 2.98 mmol)as a pale yellow
powder (0.07 g, 14.55%): mp 227–229 °C; IR (cmꢀ1): 3471, 3285,
2848, 2803, 1639, 1619, 1513, 1444, 1391, 1120, 820, 703; 1H
NMR (DMSO-d6): d 2.85 (s, 3H), 2.93 (t, J = 4.73, 4H), 3.71 (t,
J = 4.56, 4H), 5.75 (d, J = 2.33, 1H), 6.88 (d, J = 2.22, 1H), 6.59–
6.62, 6.95–7.35 (m, 8H); EI-MS: 323 [M]. Anal. Calcd for
8.1.66. N-Benzyl-2-amino-5-(piperidin-1-yl)benzamide (14d)
Compound (13d) (1.00 g, 2.94 mmol) was dissolved in CH2Cl2
(50 mL), Zn powder (0.96 g, 14.70 mmol) was added followed by
the adding of acetic acid (1.50 mL). The mixture was stirred for fur-
ther 2 h and filtered. The filterate was washed by water, dried and
evaporated to gain (14d) as a yellow powder (0.80 g, 87.77%):
mp163–165 °C; IR (cmꢀ1): 3473, 3309, 2934, 2354, 1801, 1636,
1537, 1239, 735, 696, 616; 1H NMR (CDCl3): d 1.47 (m, 2H), 1.62
(m, 4H), 1.62 (t, J = 5.13, 4H), 4.42 (d, J = 5.97, 2H), 5.94 (s, 2H),
6.61–7.33 (m, 8H), 8.74 (t, J = 5.97, 1H); EI-MS: 309 [M].
C19H21N3O2: C, 70.57; H, 6.55; N, 12.99. Found: C, 70.38; H, 6.54;
N, 13.45.
8.1.72. 2-(40-Hydroxyphenyl)-3-methyl-6-(morphilin-4-yl)-
1,2,3,4-tetrahydro-1H-quinazolin-4-one (15d)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14b) (0.15 g,
0.64 mmol), 4-hydroxybenzaldehyde (0.16 g, 1.28 mmol)as a pale
yellow powder (0.13 g, 60.09%): mp 246–248 °C; IR (cmꢀ1): 3437,
2853, 2813, 1636, 1516, 1453, 1343, 1234, 1109, 977, 841, 777,
687; 1H NMR (DMSO-d6): d 2.78 (s, 3H), 2.94 (m, 4H), 3.71 (t,
J = 4.50, 4H), 5.63 (d, J = 2.10, 1H), 6.76 (d, J = 1.80, 1H), 6.59–
6.74, 6.96–7.20 (m, 7H), 9.50 (s, 1H); EI-MS: 339 [M]. Anal. Calcd
for C19H21N3O3: C, 67.24; H, 6.24; N, 12.38. Found: C, 67.27; H,
6.53; N, 12.63.
8.1.67. N-Benzyl-2-amino-5-(morphilin-4-yl)benzamide (14e)
Following the synthetic procedure of compound (14d), the title
compound was obtained from compound (13e) (1.50 g, 4.40 mmol)
as a yellow to brown powder (1.31 g, 95.76%): mp149–151 °C; IR
(cmꢀ1): 3463, 3396, 3345, 2953, 2823, 1534, 1639, 1258, 1106,
940, 868, 825, 605; 1H NMR (CDCl3): d 2.99 (t, J = 4.65, 4H), 3.83
(t, J = 4.65, 4H), 4.62 (d, J = 5.67, 2H), 6.40–7.37 (m, 8H); EI-MS:
311 [M].
8.1.73. 2-Phenyl-3-methyl-6-(pyrrolidin-1-yl)-1,2,3,4-
tetrahydro-1H-quinazolin-4-one (15e)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14c) (0.20 g,
0.91 mmol), benzaldehyde (0.19 g, 1.83 mmol)as a yellow powder
(0.20 g, 71.34%): mp 233–235 °C; IR (cmꢀ1): 3437, 2838, 1638,
1619, 1515, 1485, 1385, 1311, 1160, 995, 810, 775, 700; 1H NMR
(DMSO-d6): d 1.91 (m, 4H), 2.87 (s, 3H), 3.13 (m, 4H), 5.69 (s,
1H), 6.86 (s, 1H), 6.58, 7.31 (m, 8H); EI-MS: 307 [M]. Anal. Calcd
for C19H21N3O: C, 74.24; H, 6.89; N, 13.67. Found: C, 74.05; H,
6.90; N, 14.04.
8.1.68. N-Benzyl-2-amino-5-(pyrrolidin-1-yl)benzamide (14f)
Following the synthetic procedure of compound (14d), the title
compound was obtained from compound (13f) (1.30 g, 4.00 mmol)
as a pale green powder (1.20 g, 100%): mp146–148 °C; IR (cmꢀ1):
3421, 3312, 2956, 1642, 1583, 1537, 1427, 1372, 1290, 1165,
987, 808; 1H NMR (CDCl3): d 2.00 (m, 4H), 3.25 (m, 4H), 4.60–
4.62 (d, J = 4.80, 2H), 6.78–7.36 (m, 8H); EI-MS: 295 [M].
8.1.69. 2-(30-Hydroxyphenyl)-3-methyl-6-(piperidin-1-yl)-
1,2,3,4-tetrahydro-1H-quinazolin-4-one (15a)
8.1.74. 2-(30-Hydroxyphenyl)-3-methyl-6-(pyrrolidin-1-yl)-
1,2,3,4-tetrahydro-1H-quinazolin-4-one (15f)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14c) (0.17 g,
The mixture of (14a) (0.17 g, 0.73 mmol), 3-hydroxybenzalde-
hyde (0.18 g, 1.46 mmol) and N,N-dimethylacetamide (DMA)
(7 mL) was stirred at room temperature for 2 h, using p-toluene
sulfonic acid as catalyst and then poured into ice-water (20 mL).
The mixture was extracted by ethyl acetate (20 mL ꢂ 3). The or-
ganic layer was purified by column chromatography (Petroleum
ether/Ethyl acetate = 2:1). The title compound was gained as a pale
yellow powder (0.16 g, 65.07%): mp 222–224 °C; IR (cmꢀ1): 3474,
3415, 3306, 2955, 2823, 1638, 1617, 1518, 1484, 1393, 1200,
1143, 890, 818, 767; 1H NMR (DMSO-d6): d 1.48 (m, 2H), 1.61
(m, 4H), 2.84 (s, 3H), 2.92 (t, J = 5.40, 4H), 5.65 (d, J = 2.40, 1H),
6.81 (d, J = 2.10, 1H), 6.55–6.75, 6.93–7.20 (m, 7H), 9.47 (s, 1H);
EI-MS: 337 [M]. Anal. Calcd for C20H23N3O2: C, 71.19; H, 6.87; N,
12.45. Found: C, 71.01; H, 6.86; N, 12.45.
0.78 mmol), 4-hydroxybenzaldehyde (0.19 g, 1.55 mmol)as
a
brown powder (0.17 g, 67.81%): mp 224–226 °C; IR (cmꢀ1): 3415,
2955, 2838, 1637, 1620, 1514, 1484, 1390, 1238, 1158, 995, 810,
769; 1H NMR (DMSO-d6): d 1.89 (m, 4H), 2.79 (s, 3H), 3.07 (m,
4H), 5.53 (s, 1H), 6.80 (s, 1H), 6.44–6.67, 7.02–7.07 (m, 7H), 9.37
(s, 1H); EI-MS: 323 [M]. Anal. Calcd for C19H21N3O2: C, 70.57; H,
6.55; N, 12.99. Found: C, 70.27; H, 6.61; N, 13.03.
8.1.75. 2-(40-Hydroxyphenyl)-3-methyl-6-(pyrrolidin-1-yl)-
1,2,3,4-tetrahydro-1H-quinazolin-4-one (15g)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14c) (0.17 g,
8.1.70. 2-(40-Hydroxyphenyl)-3-methyl-6-(piperidin-1-yl)-
1,2,3,4-tetrahydro-1H-quinazolin-4-one (15b)
0.78 mmol), 4-hydroxybenzaldehyde (0.19 g, 1.55 mmol)as a
brown powder (0.12 g, 47.86%): mp 235–240 °C; IR (cmꢀ1): 3492,
3411, 2877, 2809, 1614, 1592, 1513, 1483, 1237, 1170, 838, 810;
1H NMR (DMSO-d6): d 1.92 (m, 4H), 2.79 (s, 3H), 3.14 (m, 4H),
5.56 (s, 1H), 6.86 (s, 1H), 6.40–6.72, 7.11–7.13 (m, 7H), 9.49 (s,
1H); EI-MS: 323 [M]. Anal. Calcd for C19H21N3O2: C, 70.57; H,
6.55; N, 12.99. Found: C, 70.24; H, 6.67; C, 13.07.
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14a) (0.20 g,
0.86 mmol), 4-hydroxybenzaldehyde (0.21 g, 1.72 mmol)as a pale
yellow powder (0.21 g, 72.60%): mp 231–233 °C; IR (cmꢀ1): 3422,
2941, 2809, 1632, 1616, 1505, 1386, 1227, 1160, 1115, 835, 722,
684; 1H NMR (DMSO-d6): d 1.53 (m, 2H), 1.68 (m, 4H), 2.83 (s,
3H), 2.98 (m, 4H), 5.67 (d, J = 2.10, 1H), 6.79 (d, J = 2.10, 1H),
6.62–6.77, 6.99–7.25 (m, 7H), 9.57 (s, 1H); EI-MS: 337 [M]. Anal.
Calcd for C20H23N3O2: C, 71.19; H, 6.87; N, 12.45. Found: C,
71.14; H, 7.11; N, 12.84.
8.1.76. 2-Phenyl-3-benzyl-6-(piperidin-1-yl)-1,2,3,4-tetrahydro-
1H-quinazolin-4-one (15h)
Following the synthetic procedure of compound (15a), the title
compound was obtained from compound (14d) (0.20 g,