Pyrimidine, 2,4-dichloro-5-methyl- → Methyl 1-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 1-(2-ethynylphenyl)cyclopropanecarboxylate K2 (1.34 g, 6.67 mmol), 2,4,-dichloro-5-methylpyrimidine (1.41 g, 8.67 mmol), CuI (0.063 g, 0.33 mmol), PdCl2(PPh3)2 (0.234 g, 0.333 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.097 g, 0.33 mmol) in 1,4-dioxane (15 mL) was bubbled with N2 for 10 minutes. DIPEA (3.48 mL, 20.0 mmol) was added and the reaction mixture was stirred under N2 at 80° C. for 3 hours. The reaction mixture was cooled and the volatiles were removed in vacuo to give a black residue that was purified by column chromatography (Biotage Isolera, 2×40 g SiO2 cartridges, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the impure title compound A41 as a yellow oil (estimated 80% purity, 1.352 g, 50%). LCMS-A: rt 6.79 min; m/z 327 [M+H]+.

Provenance & Evidence