6-(2,6-Difluoro-4-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)phenyl)-5-fluoropicolinic acid (see WO2012/225062) gave 203. 1H NMR (400 MHz, DMSO-d6) δ 10.43 (s, 1H), 8.31 (dd, J=8.7, 4.0 Hz, 1H), 8.19 (t, J=8.9 Hz, 1H), 7.95 (s, 1H), 7.49 (d, J=9.3 Hz, 2H), 4.96 (dd, J=8.1, 4.0 Hz, 1H), 4.81 (d, J=1.7 Hz, 4H), 4.65-4.37 (m, 1H), 3.97-3.73 (m, 2H), 3.72 (s, 3H), 3.41-3.25 (m, 2H), 3.15 (s, 3H), 3.12-2.99 (m, 1H), 2.22-2.12 (m, 1H), 1.81-1.71 (m, 1H), 1.70-1.60 (m, 1H), 1.57-1.52 (m, 3H). LCMS (ES+) m/z 550 (M+1).

Provenance & Evidence