2-Bromopyridine → (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-1-(2-pyridinyl)pyrrolidin-3-yl]-2-piperidinecarboxamide

Participants

Reaction Conditions

Reaction Steps

Sodium hydrogen carbonate (28.6 mg) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-pyrrolidin-3-yl]-2-piperidinecarboxamide (104.9 mg) [see Example 4] and 2-bromopyridine (52.7 mg) in acetonitrile (5 ml). The reaction mixture was heated to 75° C. for 48 hours, after which time additional sodium hydrogen carbonate (28.6 mg) was added and the mixture was heated under reflux for a further 24 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water, the organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 93:7:1, by volume, dichloromethane:methanol:0.88 aqueous ammonia solution, and was then further purified by a second column eluting with 95:5, by volume, ethyl acetate:diethylamine to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-1-(2-pyridinyl)pyrrolidin-3-yl]-2-piperidinecarboxamide (11 mg) as a brown oil.

Provenance & Evidence