2-Fluoro-4-(trifluoromethyl)benzeneboronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)thiazole-4-carboxamide
Reaction equation
Br[C:2]1[S:3][C:4]([NH:32]C(=O)OC(C)(C)C)=[C:5]([C:7](=[O:31])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:30])[C:13]=2[C@@H:14]2[CH2:20][CH2:19][C@@H:18]([NH:21]C(OC(C)(C)C)=O)[C@@H:17]([F:29])[CH2:16][O:15]2)[N:6]=1.[F:40][C:41]1[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][C:42]=1B(O)O>>[NH2:32][C:4]1[S:3][C:2]([C:42]2[CH:43]=[CH:44][C:45]([C:47]([F:50])([F:49])[F:48])=[CH:46][C:41]=2[F:40])=[N:6][C:5]=1[C:7]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH3:30])[C:13]=1[C@@H:14]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[C@@H:17]([F:29])[CH2:16][O:15]1)=[O:31]Participants
3
Reactant 2
Product 1
Procedure
Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 88), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2-fluoro-4-(trifluoromethyl)phenyl)boronic acid gave 259. 1H NMR (400 MHz, DMSO-d6) δ 9.54 (s, 1H), 8.31 (q, J=9.1, 8.5 Hz, 1H), 7.93-7.84 (m, 1H), 7.83-7.71 (m, 2H), 7.61 (s, 2H), 5.17-4.82 (m, 2H), 4.31-4.14 (m, 1H), 4.08-3.93 (m, 1H), 3.77 (s, 3H), 3.51-3.37 (m, 1H), 2.19-2.05 (m, 1H), 1.98-1.81 (m, 2H), 1.75-1.67 (m, 1H). LCMS (ES+) m/z 517 (M+1).
Sources & evidence
- ORD record
- ord-d038139cbe364b0a960f09be52523475
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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