Potassium Phosphate, Tribasic → HCID 68680476, compound

Participants

Reaction Conditions

Reaction Steps

2-Chloro-N-(4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohexylmethyl)-6-trifluoromethylnicotinamide (50 mg, 0.10 mmol), cyclopropylboronic acid (44 mg, 0.51 mmol), tricyclohexylphosphine (5.7 mg, 0.02 mmol) and potassium phosphate (75 mg, 0.35 mmol) were dissolved in toluene (1 ml) and water (0.05 ml) and degassed with nitrogen for 5 minutes. Palladium acetate (2.3 mg, 0.01 mmol) was added and the mixture was heated at 100° C. for 5 hours. Palladium acetate (2.3 mg, 0.01 mmol) and tricyclohexylphosphine (5.7 mg, 0.02 mmol) were added and the reaction heated for a further 3 hours. The crude reaction mixture was diluted with dichloromethane (3 ml) and passed through a Phenomonex abw cartridge. The compound was eluted with dichloromethane (10 ml) and the filtrate was evaporated. The residue was purified by preparative plate chromatography on silica eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band, trituration of the silica with ethyl acetate, filtration and evaporation gave a colourless oil (15 mg, 30%). 1H NMR δ (ppm) (CDCl3): 7.79 (1H, d, J=7.8 Hz), 7.43 (1H, d, J=7.8 Hz), 6.00 (1H, s), 3.64 (2H, d, J=6.3 Hz), 2.97-2.89 (3H, m), 2.38-2.32 (1H, m), 2.07-1.86 (6H, m), 1.43-1.36 (2H, m), 1.28-1.14 (5H, m), 1.07-1.05 (2H, m), 0.78-0.68 (3H, m), 0.52 (2H, q, J=5.9 Hz), 0.42 (2H, q, J=5.3 Hz), 0.05 (2H, dd, J=0.0, 4.8 Hz). MS (n/e)=499.

Provenance & Evidence