6-(2,6-Difluoro-4-methoxyphenyl)-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-methoxyphenyl)-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-methoxyphenyl)-5-fluoropicolinic acid (see WO2010/56576) gave 187 as a white solid (22 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 10.40 (s, 1H), 8.31 (dd, J=8.6, 4.0 Hz, 1H), 8.21 (s, 1H), 7.71-7.63 (m, 1H), 6.64 (d, J=10.1 Hz, 2H), 4.84-4.73 (m, 2H), 4.07-3.89 (m, 3H), 3.87 (s, 3H), 3.77 (s, 3H), 3.41 (dd, J=23.1, 9.5 Hz, 1H), 2.67 (br s, 1H), 2.15-2.08 (m, 1H), 2.08-1.94 (m, 1H), 1.95-1.84 (m, 1H), 1.85-1.73 (m, 1H). LCMS (ES+) m/z 494 (M+1).

Provenance & Evidence