Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → Methyl 4-{4-[({[5-amino-2-(cyclopropylsulfanyl)phenyl]methyl}(methyl)carbamoyl)[(1 {bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]methyl]-2,6-dimethylphenyl}-3-hydroxybutanoate

Participants

Reaction Conditions

Reaction Steps

2C (100 mg, 0.376 mmol), Intermediate 3 (142 mg, 0.376 mmol), and glyoxylic acid monohydrate (34.6 mg, 0.376 mmol) were dissolved in acetonitrile (1.5 mL)/DMF (1.500 mL) and heated at 80° C. for 2 h. A solution of Intermediate 6 (106 mg, 0.376 mmol)) and TEA (0.157 mL, 1.127 mmol) in DMF (1.500 mL) was added followed by BOP (183 mg, 0.413 mmol) as a solid. 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 material was purified by column chromatography (0 to 100% EtOAc in hexanes then elute with 20% MeOH in dichloromethane) to yield 2D (210 mg, 0.248 mmol, 66.1% yield) as a yellow solid. MS (ESI) m/z: 846.7 (M+H)+.

Provenance & Evidence