Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → tert-Butyl N-(6-{[({[5-amino-2-(cyclopropanesulfonyl)phenyl]methyl}(methyl)carbamoyl)({2-fluoro-4-[(2R)-1-hydroxypropan-2-yl]-5-methoxyphenyl})methyl]amino}-7-fluoroisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamate

Participants

Reaction Conditions

Reaction Steps

25C (0.075 g, 0.329 mmol), Intermediate 4 (0.124 g, 0.329 mmol) and glyoxylic acid monohydrate (0.033 g, 0.362 mmol) were dissolved in acetonitrile (1 mL)/DMF (1.000 mL) and heated at 80° C. for 3 h. A solution of Intermediate 8 (0.103 g, 0.329 mmol)) and TEA (0.138 mL, 0.987 mmol) in DMF (1.000 mL) was added followed by BOP (0.160 g, 0.362 mmol). The reaction mixture was stirred at rt for 3 h. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (loading in chloroform, 0% to 100% ethyl acetate in hexane over 15 min using a 12 g silica gel cartridge) to yield 25D (155 mg, 0.185 mmol, 56.1% yield) as a yellow solid. MS (ESI) m/z: 840.4 (M+H)+.

Provenance & Evidence