4-(Difluoromethoxy)benzyl Bromide → 2-(3-(4-(difluoromethoxy)benzyl)-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 883145Notes

Reaction equation

HRID 883145 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH:10]([F:12])[F:11])=[CH:5][CH:4]=1.[F:13][C:14]1[CH:35]=[CH:34][C:17]([CH2:18][NH:19][C:20]([C:22]2[S:26][C:25]([N:27]3[CH2:31][CH2:30][CH2:29][C:28]3=[O:32])=[N:24][C:23]=2[CH3:33])=[O:21])=[CH:16][CH:15]=1>>[F:11][CH:10]([F:12])[O:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][CH:29]2[CH2:30][CH2:31][N:27]([C:25]3[S:26][C:22]([C:20]([NH:19][CH2:18][C:17]4[CH:16]=[CH:15][C:14]([F:13])=[CH:35][CH:34]=4)=[O:21])=[C:23]([CH3:33])[N:24]=3)[C:28]2=[O:32])=[CH:4][CH:5]=1

Participants

3

Reactant 2

HCID 27370014-(Difluoromethoxy)benzyl BromideHCID 16954475HCID 16954475, compound

Product 1

HCID 248015072-(3-(4-(difluoromethoxy)benzyl)-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 31%

Procedure

Following the procedure as described in Example 2, making variation as required to use 1-(bromomethyl)-4-(difluoromethoxy)benzene in place of 1-(bromomethyl)-4-(trifluoromethyl)benzene to react with N-(4-fluorobenzyl)-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide, the title compound was obtained as a white solid in 31% yield: mp 143-145° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.34-7.22 (m, 2H), 7.16 (d, J=8.4 Hz, 2H), 7.06-6.93 (m, 4H), 6.45 (t, J=73.9 Hz, 1H), 6.08 (t, J=5.6 Hz, 1H), 4.51 (d, J=5.6 Hz, 2H), 4.09-3.99 (m, 1H), 3.91-3.78 (m, 1H), 3.25-3.12 (m, 1H), 3.05-2.94 (m, 1H), 2.83-2.73 (m, 1H), 2.59 (s, 3H), 2.32-2.18 (m, 1H), 1.98-1.81 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 174.7, 162.3, 162.2, 160.6, 155.4, 152.7, 149.9, 135.4, 133.8, 130.3, 129.6, 119.8, 115.6, 112.4, 45.9, 44.3, 43.3, 35.6, 24.2, 17.2; MS (ES+) m/z 490.3 (M+1).

Sources & evidence

ORD record
ord-85370dec2d934fc68e630cb414460353
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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