1,1'-Carbonyldiimidazole → 3-(1-Benzylpiperidin-4-yl)-7-fluoro-3,4-dihydroquinazolin-2(1H)-one
Reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:15]=1[CH2:16][NH:17][CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:19]1>O1CCCC1>[CH2:24]([N:21]1[CH2:22][CH2:23][CH:18]([N:17]2[CH2:16][C:15]3[C:14](=[CH:34][C:33]([F:35])=[CH:32][CH:31]=3)[NH:13][C:1]2=[O:2])[CH2:19][CH2:20]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1Participants
4
Procedure
1,1′-Carbonyldiimidazole (6.92 g, 42.7 mmol) was added to a solution of N-(2-amino-4-fluorobenzyl)-1-benzylpiperidin-4-amine (8.64 g, 30.2 mmol) in dry tetrahydrofuran (150 mL) at 0° C. in one portion. After 5 min, the mixture was allowed to warm to room temperature and stirred for 3 h. The reaction was partitioned between water/diethyl ether (200 mL/200 mL). After separation, the aqueous solution was extracted with diethyl ether (200 mL). The combined organic solution was washed with brine (100 mL), dried over magnesium sulfate, and concentrated in vacuo to afford a light yellow solid which was triturated with diethyl ether (3×10 mL) to give the title compound as a white solid (3.41 g, 36% yield). 1H-NMR (CDCl3, 400 MHz) δ 7.40-7.18 (m, 5H), 6.92-6.82 (m, 1H), 6.75 (dd, J=8.2, 2.6, 1H), 6.66 (dd, J=8.8, 4.8, 1H), 4.48-4.34 (m, 1H), 4.03 (s, 2H), 3.53 (s, 2H), 2.98 (d, J=11.2, 2H), 2.37-2.12 (m, 2H), 1.99-1.82 (m, 2H), 1.67 (d, J=11.2, 2H); Mass spec.: 340.03 (MH+).