Ethyl Acetate → Benzyl[2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate

Participants

Reaction Steps

A solution of cyclopropylamine (261.9 μL, 3.70 mmol) in dry THF (2 mL) under an inert atmosphere was chilled in an ice-water bath and freshly titrated isopropylmagnesium chloride (1.46 M in THF, 1.27 mL, 1.85 mmol) was added. A portion of this chloromagnesium cyclopropylamide solution (0.524 M in THF, 2.12 mL, 1.11 mmol) was added via syringe to a stirred solution of methyl 3-[3-[1-[2-[2-[(benzyloxycarbonyl)methylamino]ethoxy]phenyl]cyclopropylamino]-5-bromo-2-oxo-1(2H)-pyrazinyl]-5-fluoro-4-methylbenzoate (Preparation 4d, 125.7 mg, 185 μmol) in dry THF (2 mL) under an inert atmosphere. After 30 min, ethyl acetate (1 mL) was added before the reaction mixture was poured into ice-cold saturated aq. ammonium chloride (10 mL) and extracted with diethyl ether (3×10 mL). The organic extracts were combined, washed with brine (30 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC on silica, eluting with ethyl acetate/isohexane/methanol (50:50:1 v/v), to afford benzyl [2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate (79.4 mg) as a white foam.

Provenance & Evidence