6-(2,6-Difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid → N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinamide

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Reaction Steps

Following the procedure for Example 111 starting from tert-butyl ((3S,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 80), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 192. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.26 (dd, J=8.6, 4.0 Hz, 1H), 8.11 (t, J=8.9 Hz, 1H), 7.91 (s, 1H), 7.01-6.91 (m, 2H), 4.82 (dd, J=10.3, 3.8 Hz, 1H), 4.32-4.12 (m, 3H), 4.05-3.85 (m, 2H), 3.75 (s, 3H), 3.74-3.65 (m, 2H), 3.32 (s, 3H), 3.06 (dd, J=16.5, 7.8 Hz, 1H), 2.10-2.02 (m, 1H), 1.82-1.57 (m, 5H). LCMS (ES+) m/z 538 (M+1).

Provenance & Evidence