6-(2,6-Difluoro-4-(methoxymethyl)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-(methoxymethyl)phenyl)-5-fluoropicolinamide

Participants

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-(methoxymethyl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 199. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.29 (dd, J=8.6, 4.0 Hz, 1H), 8.15 (t, J=8.8 Hz, 1H), 7.91 (s, 1H), 7.24 (d, J=9.0 Hz, 2H), 4.81 (dd, J=10.3, 3.7 Hz, 1H), 4.53 (s, 2H), 4.31-4.07 (m, 1H), 4.02-3.83 (m, 2H), 3.75 (s, 3H), 3.36 (s, 3H), 3.11-2.98 (m, 1H), 2.10-2.00 (m, 1H), 1.82-1.57 (m, 3H). LCMS (ES+) m/z 508 (M+1).

Provenance & Evidence