5-((Tert-butoxycarbonyl)amino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid → 5-Amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-fluorophenyl)thiazole-4-carboxamide
Reaction equation
[F:1][C@@H:2]1[C@H:8]([NH:9]C(=O)OC(C)(C)C)[CH2:7][CH2:6][C@@H:5]([C:17]2[N:21]([CH3:22])[N:20]=[CH:19][C:18]=2[N+:23]([O-])=O)[O:4][CH2:3]1.C(OC([NH:33][C:34]1[S:38][C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])=[N:36][C:35]=1[C:46](O)=[O:47])=O)(C)(C)C>>[NH2:33][C:34]1[S:38][C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])=[N:36][C:35]=1[C:46]([NH:23][C:18]1[CH:19]=[N:20][N:21]([CH3:22])[C:17]=1[C@@H:5]1[CH2:6][CH2:7][C@@H:8]([NH2:9])[C@@H:2]([F:1])[CH2:3][O:4]1)=[O:47]Participants
Reactant 2
Product 1
Procedure
Following the procedure for Example 111 starting from tert-butyl ((3R,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 24), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 5-(tert-butoxycarbonylamino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid (Example 7) gave 186 as the hydrochloride salt as a white solid (38 mg, 71%). 1H NMR (400 MHz, d6-DMSO) δ 9.47 (s, 1H), 8.60-8.40 (m, 3H), 8.19-8.13 (m, 1H), 7.71 (s, 1H), 7.49-7.35 (m, 3H), 5.40-5.23 (m, 1H), 4.87 (d, J=10.5 Hz, 1H), 4.28 (ddd, J=32.0, 14.5, 4.7 Hz, 1H), 4.07 (ddd, J=23.4, 14.5, 2.8 Hz, 1H), 3.80 (s, 3H), 3.78-3.60 (m, 1H), 2.19-1.82 (m, 4H). LCMS (ES+) m/z 449 (M+1). Alkyl NH2 not observed.
Sources & evidence
- ORD record
- ord-17c672a245624f51942a24e8e46ef1ee
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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