4-(Difluoromethoxy)benzyl Bromide → N-benzyl-2-(3-(4-(difluoromethoxy)benzyl)-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide
Reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:20][CH2:19][CH2:18][C:17]2=[O:21])=[N:13][C:12]=1[CH3:22])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH:32]([F:34])[F:33])=[CH:27][CH:26]=1>>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:20][CH2:19][CH:18]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH:32]([F:33])[F:34])=[CH:29][CH:30]=3)[C:17]2=[O:21])=[N:13][C:12]=1[CH3:22])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Procedure
Following the procedure as described in Example 2, making variation as required to use N-benzyl-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide in place of N-(4-fluorobenzyl)-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide to react with 1-(bromomethyl)-4-(difluoromethoxy)benzene in place of 1-(bromomethyl)-4-(trifluoromethyl)benzene, the title compound was obtained as a white solid in 27% yield: mp 132-133° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.41-7.24 (m, 5H), 7.18 (d, J=8.2 Hz, 2H), 7.03 (d, J=8.2 Hz, 2H), 6.46 (dt, J=73.9, 1.0 Hz, 1H), 5.94 (t, J=5.5 Hz, 1H), 4.57 (d, J=5.5 Hz, 2H), 4.11-3.98 (m, 1H), 3.93-3.81 (m, 1H), 3.28-3.16 (m, 1H), 3.08-2.93 (m, 1H), 2.80 (dd, J=13.7, 8.8 Hz, 1H), 2.62 (s, 3H), 2.33-2.19 (m, 1H), 1.99-1.84 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 174.6, 162.3, 155.3, 152.7, 137.8, 135.4, 130.3, 128.8, 127.9, 127.7, 119.9, 119.5, 118.7, 115.9, 45.9, 44.4, 44.1, 35.6, 24.2, 17.3; MS (ES+) m/z 472.3 (M+1).
Sources & evidence
- ORD record
- ord-bf1c19726eec44189c158852c8624c11
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08236835B2
Reaction notes
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