Diisopropylethylamine → tert-Butyl N-(6-{[({[5-amino-2-(cyclopropanesulfonyl)phenyl]methyl}(methyl)carbamoyl)({4-[(2R)-1-fluoro-3-hydroxypropan-2-yl]-3-methylphenyl})methyl]amino}isoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamate

Participants

Reaction Steps

A mixture of Intermediate 1 1080 (0.076 g, 0.212 mmol), 24D (0.045 g, 0.212 mmol) and glyoxylic acid monohydrate (0.020 g, 0.218 mmol) suspended in DMF (0.5 mL) and acetonitrile (1.5 mL) was heated at 80° C. in an oil bath for 2.0 h. After it was cooled to rt, Intermediate 8 (0.066 g, 0.212 mmol) and DIEA (0.185 mL, 1.061 mmol) was added, followed by BOP (0.094 g, 0.212 mmol). The mixture was left stirring at rt overnight. The solvent was removed under reduced pressure, the crude residue was redissolved in dichloromethane and washed with brine (3×) and dried over sodium sulfate. The crude product was purified by flash chromatography (0-100% EtOAc/hexanes) to give 24E (0.103 g, 0.128 mmol, 60.2% yield). MS (ESI) (m/z): 806.3 (M+H)+.

Provenance & Evidence