5-((Tert-butoxycarbonyl)amino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid → 5-Amino-N-[5-[(2S,5R,6R)-5-amino-6-methoxy-oxepan-2-yl]-1-methyl-pyrazol-4-yl]-2-(2-fluorophenyl)thiazole-4-carboxamide

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Reaction Steps

Following the procedure for Example 111 starting from tert-butyl ((3R,4R,7S)-3-methoxy-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 93), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 5-(tert-butoxycarbonylamino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid (Example 7) gave 183 as the hydrochloride salt as a dark salmon pink solid (68 mg, 45%). 1H NMR (400 MHz, d6-DMSO) δ 9.47 (s, 1H), 8.18-8.09 (m, 5H), 7.74 (s, 1H), 7.52-7.36 (m, 4H), 4.96 (dd, J=9.9, 2.8 Hz, 1H), 4.19 (dd, J=13.6, 5.0 Hz, 1H), 4.00 (dd, J=13.6, 5.3 Hz, 1H), 3.86 (d, J=4.5 Hz, 1H), 3.78 (s, 3H), 3.62-3.49 (m, 1H), 3.33 (s, 3H), 2.14-1.97 (m, 2H), 1.98-1.74 (m, 2H). LCMS (ES+) m/z 461 (M+1).

Provenance & Evidence