5-(Tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acid → 5-Amino-N-[5-[(2S,5R,6R)-5-amino-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2,3-difluorophenyl)thiazole-4-carboxamide

Participants

Reaction Steps

Following the procedure for Example 111 starting from tert-butyl N-[(3S,4R,7S)-3-fluoro-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-yl]carbamate (Intermediate 88), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 5-(tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acid (Example 25) gave 181 as the hydrochloride salt as a pale pink solid (30 mg, 38% over three steps). 1H NMR (400 MHz, d6-DMSO) δ 9.42 (s, 1H), 8.54-8.41 (m, 4H), 7.96-7.89 (m, 1H), 7.67 (s, 1H), 7.50-7.39 (m, 3H), 5.28 (m, 1H), 4.84 (d, J=10.4 Hz, 1H), 4.33-4.17 (m, 1H), 4.11-3.99 (m, 1H), 3.78 (s, 3H), 3.74-3.52 (m, 1H), 2.16-1.81 (m, 4H). LCMS (ES+) m/z 467 (M+1).

Provenance & Evidence