5-((Tert-butoxycarbonyl)amino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid → 5-Amino-N-[5-[(2S,5R,6R)-5-amino-6-methoxy-oxepan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2-fluorophenyl)thiazole-4-carboxamide
Reaction equation
[CH3:1][O:2][C@@H:3]1[C@H:9]([NH:10]C(=O)OC(C)(C)C)[CH2:8][CH2:7][C@@H:6]([C:18]2[N:19]([CH3:26])[N:20]=[CH:21][C:22]=2[N+:23]([O-])=O)[O:5][CH2:4]1.C(OC([NH:34][C:35]1[S:39][C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[F:46])=[N:37][C:36]=1[C:47](O)=[O:48])=O)(C)(C)C>>[NH2:34][C:35]1[S:39][C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[F:46])=[N:37][C:36]=1[C:47]([NH:23][C:22]1[CH:21]=[N:20][N:19]([CH3:26])[C:18]=1[C@@H:6]1[CH2:7][CH2:8][C@@H:9]([NH2:10])[C@@H:3]([O:2][CH3:1])[CH2:4][O:5]1)=[O:48]Participants
Reactant 2
Product 1
Procedure
Following the procedure for Example 111 starting from tert-butyl ((3R,4R,7S)-3-methoxy-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 93), 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 183 as the hydrochloride salt as a dark salmon pink solid (68 mg, 45%). 1H NMR (400 MHz, d6-DMSO) δ 9.47 (s, 1H), 8.18-8.09 (m, 5H), 7.74 (s, 1H), 7.52-7.36 (m, 4H), 4.96 (dd, J=9.9, 2.8 Hz, 1H), 4.19 (dd, J=13.6, 5.0 Hz, 1H), 4.00 (dd, J=13.6, 5.3 Hz, 1H), 3.86 (d, J=4.5 Hz, 1H), 3.78 (s, 3H), 3.62-3.49 (m, 1H), 3.33 (s, 3H), 2.14-1.97 (m, 2H), 1.98-1.74 (m, 2H). LCMS (ES+) m/z 461 (M+1).
Sources & evidence
- ORD record
- ord-fe60cf22319c4d0eb6182bc7fac9c7f1
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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