2-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide → 4-methyl-2-(2-oxo-3-(4-(trifluoromethoxy)benzyl)pyrrolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide
Reaction equation
[F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][CH:9]2[CH2:13][CH2:12][NH:11][C:10]2=[O:14])=[CH:6][CH:5]=1.Br[C:20]1[S:21][C:22]([C:26]([NH:28][CH2:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[O:27])=[C:23]([CH3:25])[N:24]=1>>[CH3:25][C:23]1[N:24]=[C:20]([N:11]2[CH2:12][CH2:13][CH:9]([CH2:8][C:7]3[CH:15]=[CH:16][C:4]([O:3][C:2]([F:17])([F:1])[F:18])=[CH:5][CH:6]=3)[C:10]2=[O:14])[S:21][C:22]=1[C:26]([NH:28][CH2:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1)=[O:27]Participants
Procedure
Following the procedure as described in Example 8, making variations as required to use 3-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one in place of 3-(4-fluorobenzyl)pyrrolidin-2-one to react with 2-bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide, the title compound was obtained as a white solid in 34% yield: mp 158-160° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.49 (d, J=4.0 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.31-7.06 (m, 5H), 6.43 (t, J=5.7 Hz, 1H), 4.58 (d, J=5.7 Hz, 2H), 4.06 (ddd, J=11.5, 8.0, 3.1 Hz, 1H), 3.86 (td, J=11.5, 8.0 Hz, 1H), 3.23 (dd, J=13.9, 4.4 Hz, 1H), 3.08-2.94 (m, 1H), 2.83-2.74 (m, 1H), 2.60 (s, 3H), 2.34-2.19 (m, 1H), 1.94-1.87 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 174.6, 162.5, 155.4, 153.2, 149.3, 148.9, 148.0, 138.1, 136.9, 135.7, 133.9, 130.3, 123.7, 121.2, 118.3, 45.9, 44.3, 41.5, 35.7, 24.3, 17.3; MS (ES+) m/z 491.3 (M+1).
Sources & evidence
- ORD record
- ord-9926ae2f3457482ab8f2973178711da9
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08236835B2
Reaction notes
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