6-(2,6-Difluoro-4-(2-methoxyethoxy)phenyl)-5-fluoropicolinic acid → N-(5-((2S,5R,6S)-5-Amino-6-hydroxyoxepan-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 ((3S,4R,7S)-3-hydroxy-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 94), 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 191 as a white solid (73 mg, 71%). 1H NMR (400 MHz, d6-DMSO) δ 10.22 (s, 1H), 8.25 (dd, J=8.6, 4.0 Hz, 1H), 8.12 (t, J=8.9 Hz, 1H), 7.82 (s, 1H), 6.97 (d, J=10.2 Hz, 2H), 4.79 (dd, J=10.8, 3.4 Hz, 2H), 4.26-4.20 (m, 2H), 3.90-3.67 (m, 4H), 3.73-3.67 (m, 2H), 3.63 (dd, J=12.8, 5.8 Hz, 1H), 3.62-3.02 (m, 3H), 2.73-2.64 (m, 1H), 2.00-1.92 (m, 1H), 1.92-1.79 (m, 1H), 1.79-1.72 (m, 1H), 1.55-1.42 (m, 1H). Alkyl NH2 not observed. LCMS (ES+) m/z 536 (M+1).

Provenance & Evidence