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

Participants

Reaction Steps

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 6-(2,6-difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 189 as a white solid (19 mg, 50%). 1H NMR (400 MHz, d6-DMSO) δ 10.45 (s, 1H), 8.26 (dd, J=8.6, 3.9 Hz, 1H), 8.19-8.09 (m, 1H), 7.95 (s, 1H), 7.03 (d, J=10.5 Hz, 2H), 4.95 (dd, J=8.3, 3.6 Hz, 1H), 4.69 (s, 1H), 4.57 (s, 1H), 4.24 (t, J=4.2 Hz, 2H), 3.98-3.78 (m, 2H), 3.73 (s, 3H), 3.70 (t, J=4.2 Hz, 2H), 3.30 (s, 3H), 3.15 (m, 1H), 2.20-2.11 (m, 1H), 1.89-1.72 (m, 2H), 1.72-1.62 (m, 1H), 1.59-1.50 (m, 1H). LCMS (ES+) m/z 538 (M+1).

Provenance & Evidence