Diisopropylethylamine → 2-tert-butyl-N-[(3S,5R)-5-(1-hydroxycyclohexyl)piperidin-3-yl]-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)pyrimidine-5-carboxamide dihydrochloride

Participants

Reaction Steps

tert-Butyl (3R,5S)-3-(1-hydroxycyclohexyl)-5-[(2-methylpropyl)amino]piperidine-1-carboxylate (0.92 g) and N,N-diisopropylethylamine (1.0 g) were dissolved in 1,2-dichloroethane (10 ml), 2-tert-butyl-4-[(3-methoxypropyl)amino]pyrimidine-5-carbonyl chloride (0.74 g) was added under ice-cooling, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated, and diluted with aqueous calcium carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml), and the mixture was stirred at room temperature for 0.5 hr. The reaction mixture was concentrated and purified by HPLC. The concentrate was dissolved in 4 N hydrogen chloride-ethyl acetate (1 ml) and concentrated to give the object compound (5.9 mg).

Provenance & Evidence