Triethylamine → Methyl (+/-)-3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3-cyclobutylpropanoate

Participants

Reaction Conditions

Reaction Steps

To a racemic solution of methyl 3-amino-3-cyclobutylpropanoate, 49a, (0.354 g, 2.252 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (0.414 g, 2.477 mmol) in THF (10 mL) and ethanol (1 mL) was added triethylamine (0.628 mL, 4.504 mmol). The reaction mixture was heated and stirred at 70° C. for 5 hours. The mixture was filtered and the filtrate was concentrated in vacuo to approximately 5 mL final volume. The crude residue was purified via silica gel chromatography (0-100% EtOAC/hexanes gradient) to afford 289 mg (45%) of the desired product: 1H NMR (300 MHz, CDCl3) δ 7.87 (s, 1H), 5.80 (s, 1H), 4.71-4.38 (m, 1H), 3.68 (s, 3H), 2.84-2.37 (m, 3H), 2.23-1.67 (m, 6H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=3.08 minutes (M+H) 287.98.

Provenance & Evidence