6-(2,6-difluoro-4-((tetrahydro-2H-pyran-4-yl)oxy)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-((tetrahydro-2H-pyran-4-yl)oxy)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-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 197. 1H NMR (400 MHz, DMSO-d6) δ 10.19 (s, 1H), 8.25 (dd, J=8.7, 4.0 Hz, 1H), 8.11 (t, J=8.9 Hz, 1H), 7.91 (s, 1H), 6.99 (d, J=10.2 Hz, 2H), 4.82 (dd, J=10.4, 3.7 Hz, 1H), 4.77-4.66 (m, 1H), 4.21 (ddd, J=49.1, 7.8, 2.9 Hz, 1H), 4.10-3.90 (m, 2H), 3.90-3.80 (m, 2H), 3.75 (s, 3H), 3.51 (ddd, J=12.0, 9.4, 2.8 Hz, 2H), 3.14-3.01 (m, 1H), 2.10-1.97 (m, 3H), 1.85-1.55 (m, 5H). LCMS (ES+) m/z 564 (M+1).

Provenance & Evidence