6-Bromo-5-fluoropicolinic Acid → tert-butyl N-[(3R,4R,7S)-7-[4-[(6-bromo-5-fluoro-pyridine-2-carbonyl)amino]-2-methyl-pyrazol-3-yl]-3-methoxy-oxepan-4-yl]carbamate
Reaction equation
[CH3:1][O:2][C@@H:3]1[C@H:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[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.[Br:27][C:28]1[N:33]=[C:32]([C:34](O)=[O:35])[CH:31]=[CH:30][C:29]=1[F:37]>>[Br:27][C:28]1[N:33]=[C:32]([C:34]([NH:23][C:22]2[CH:21]=[N:20][N:19]([CH3:26])[C:18]=2[C@H:6]2[O:5][CH2:4][C@H:3]([O:2][CH3:1])[C@H:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8][CH2:7]2)=[O:35])[CH:31]=[CH:30][C:29]=1[F:37]Participants
Reactant 2
Product 1
Procedure
Following the procedure for Example 65, starting from tert-butyl N-[(3R,4R,7S)-3-methoxy-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-yl]carbamate (intermediate 93) and replacing 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid with 6-bromo-5-fluoro-pyridine-2-carboxylic acid (see US2010/56576 A1) gave tert-butyl N-[(3R,4R,7S)-7-[4-[(6-bromo-5-fluoro-pyridine-2-carbonyl)amino]-2-methyl-pyrazol-3-yl]-3-methoxy-oxepan-4-yl]carbamate (contaminated with tetramethylurea) as a clear oil (169 mg, 30% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.37 (s, 1H), 8.26-8.17 (m, 2H), 7.63-7.55 (m, 1H), 5.02 (br s, 1H), 4.96 (dd, J=9.0, 3.6 Hz, 1H), 4.32 (dd, J=13.2, 4.4 Hz, 1H), 4.05-3.94 (m, 2H), 3.85-3.80 (m, 1H), 3.78 (s, 3H), 3.47 (s, 3H), 2.10-1.91 (m, 3H), 1.86-1.78 (m, 1H), 1.45 (s, 9H).
Sources & evidence
- ORD record
- ord-98ad4f2389054933a899640a02283871
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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