2-(Bromomethyl)-1,4-difluorobenzene → N-benzyl-2-(3-(2,5-difluorobenzyl)-2-oxopiperidin-1-yl)-4-methylthiazole-5-carboxamide

HRID 883153Notes

Reaction equation

HRID 883153 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[F:33]>>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH:18]([CH2:25][C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=3[F:33])[C:17]2=[O:22])=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 5228302-(Bromomethyl)-1,4-difluorobenzeneHCID 24799232N-benzyl-4-methyl-2-(2-oxopiperidin-1-yl)thiazole-5-carboxamide

Product 1

HCID 24801157N-benzyl-2-(3-(2,5-difluorobenzyl)-2-oxopiperidin-1-yl)-4-methylthiazole-5-carboxamideYield 32%

Procedure

Following the procedure as described in Example 2, making variation as required to use N-benzyl-4-methyl-2-(2-oxopiperidin-1-yl)thiazole-5-carboxamide in place of N-(4-fluorobenzyl)-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide to react with 2-(bromomethyl)-1,4-difluorobenzene in place of 1-(bromomethyl)-4-(trifluoromethyl)benzene, the title compound was obtained as a white solid in 32% yield: mp 144-145° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.37-7.22 (m, 5H), 7.02-6.81 (m, 3H), 6.01 (t, J=5.6 Hz, 1H), 4.56 (d, J=5.6 Hz, 2H), 4.32-4.20 (m, 1H), 4.03-3.94 (m, 1H), 3.47-3.37 (m, 1H), 2.90-2.73 (m, 2H), 2.63 (s, 3H), 2.12-1.98 (m, 1H), 1.96-1.75 (m, 2H), 1.64-1.45 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 171.5, 162.6, 160.2, 158.6, 157.3, 156.9, 152.2, 137.9, 128.8, 127.9, 127.5, 119.6, 117.7, 116.3, 114.7, 47.9, 44.1, 43.0, 30.6, 24.9, 21.3, 17.3; MS (ES+) m/z 456.2 (M+1).

Sources & evidence

ORD record
ord-f76740d104c74610811c75ef8daaf240
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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