6-(2,6-Difluoro-4-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 202. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.32 (dd, J=8.7, 4.0 Hz, 1H), 8.17 (t, J=8.9 Hz, 1H), 7.94 (s, 1H), 7.42 (d, J=9.3 Hz, 2H), 4.87-4.75 (m, 5H), 4.17 (ddt, J=49.0, 6.1, 2.6 Hz, 1H), 4.03-3.84 (m, 2H), 3.75 (s, 3H), 3.14 (s, 3H), 3.12-2.98 (m, 1H), 2.11-2.00 (m, 1H), 1.80-1.57 (m, 3H). LCMS (ES+) m/z 550 (M+1).

Provenance & Evidence