Hydrochloric Acid → (1R)-1-[[[(1R,2R,4R)-2-[[[(1S)-1-[[[(1S)-1-Cyclohexyl-2-(methylamino)-2-oxoethyl]amino]carbonyl]-2,2-dimethylpropyl]amino]carbonyl]-4-hydroxycyclopentyl]carbonyl]amino]-2-ethenyl-cyclopropanecarboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

Compound 72 (60 mg, 0.14 mmol) was dissolved in dioxane (3.5 mL) and H2O (2.5 mL) and the solution was cooled to 0° C. LiOH (1 M, 280 □L, 0.28 mmol) was added dropwise during 5 min, after which the reaction mixture was stirred at 0° C. for 40 min. The pH was adjusted to 7 using 1 M HCl, and the solvents were evaporated. The residue was suspended in DMF (5 mL) and 1-amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester (32 mg, 0.17 mmol), and DIEA (146 □L, 0.84 mmol) were added. After cooling to 0° C. HATU (64 mg, 0.17 mmol) was added and the mixture was stirred at 0° C. for 1 h and at rt for 1 h. The solvent was evaporated and the product was purified using flash column chromatography (EtOAc/MeOH 9:1) to give compound 73 (67 mg, 82%) as a white solid.

Provenance & Evidence