Nitrogen → tert-Butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

A solution of 2-1 (100 mg, 0.35 mmol), tert-butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate (119 mg, 0.52 mmol; for preparation, see D. C. Pryde et al. J. Med. Chem. 2006, 49, 4409-4424), 1 M potassium tert-butoxide (1.03 mL in THF) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.6 mg, 0.035 mmol) in 2-Methyl-2-butanol (1.7 ml) was purged with N2 for 5 min. Tris(dibenzylideneacetone)-dipalladium(0) (31.6 mg, 0.035 mmol) was added and the mixture was heated at 60° C. for 1 hour. The reaction was cooled to room temperature and diluted with ethyl acetate and sat. NaHCO3. The organic phase was washed with water, brine and concentrated. The residue was purified by flash column chromatography using a 20-60% ethyl acetate/hexane gradient gave 2-2 as a colorless oil (117 mg, 70%). MS (M+H)+: observed=483.10, calculated=483.21.

Provenance & Evidence