Dichloromethane → HCID 72721008, compound

Participants

Reaction Steps

To a suspension of (3S)-ethyl 3-(3-bromo-5-(1-(difluoromethyl)cyclopropyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate (from step 2 above) (0.635 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (135 mg, 3.217 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a pale yellow crystalline residue. The residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL) to remove the urea. The aqueous layer was neutralized with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale yellow viscous residue. The crude residue was purified by reverse-phase preparative HPLC on a Biotage 40+M (100 g) C18HS column and a gradient 10-60% acetonitrile in water containing 0.05% TFA to give the desired product, after lyophilization, as a colorless lyophilized powder (94.0 mg). LC-MS analysis of the product shows the desired product's mass: m/z 624 (79BrM+H) and m/z 626 (81BrM+H); Calcd for C26H28BrF2N5O6: 624.43.

Provenance & Evidence