Dichloromethane → HCID 72950694, compound

Participants

Reaction Steps

To a suspension of (3S)-ethyl 3-(3-chloro-5-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate (from step 2 above) (0.785 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (165 mg, 3.932 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a yellow-orange viscous residue and the residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL) for 15 min. The aqueous layer was separated, acidified with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale 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 afford the desired product, after lyophilization, as a colorless lyophilized powder (277.7 mg). LC-MS analysis of the residue shows the desired product: (3S)-3-(3-chloro-5-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid's mass: m/z 600 (35ClM+H), and m/z 602 (37ClM+H); Calcd for C26H29ClF3N5O6: 599.99.

Provenance & Evidence