5-((Tert-butoxycarbonyl)amino)-2-(2,5-difluorophenyl)thiazole-4-carboxylic acid → 5-amino-N-(5-((4S,5S)-4-amino-5-fluoroazepan-1-yl)-1-cyclopropyl-1H-pyrazol-4-yl)-2-(2,5-difluorophenyl)thiazole-4-carboxamide

Participants

Reaction Steps

Following the procedure for Example 107 starting from N-(1-(4-amino-1-cyclopropyl-1H-pyrazol-5-yl)-5-fluoroazepan-4-yl)-2,2,2-trifluoroacetamide and 5-(tert-butoxycarbonyl-amino)-2-(2,5-difluorophenyl)thiazole-4-carboxylic acid gave 276 as the monoformate salt as an off-white solid (170 mg, 40% over two steps). 1H NMR (400 MHz, d4-MeOD) δ 8.54 (s, 1H), 8.06 (ddd, J=9.4, 5.8, 3.2 Hz, 1H), 7.39 (s, 1H), 7.28 (td, J=9.9, 4.4 Hz, 1H), 7.19-7.11 (m, 1H), 4.86 (dtd, J=49.0, 9.3, 3.6 Hz, 1H), 3.62-3.49 (m, 2H), 3.50-3.38 (m, 4H), 2.45-2.31 (m, 1H), 2.26-2.06 (m, 2H), 1.99-1.86 (m, 1H), 1.21-1.12 (m, 2H), 1.15-1.05 (m, 2H). LCMS (ES+) m/z 492 (M+1)

Provenance & Evidence