3-(Methylthio)propylamine → methyl (3R*,5S*)-5-[[(2-tert-butyl-4-{[3-(methylthio)propyl]amino}pyrimidin-5-yl)carbonyl](isobutyl)amino]piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-tert-butyl 3-methyl (3R*,5S*)-5-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](isobutyl)amino}piperidine-1,3-dicarboxylate (51.1% mg) and diisopropylethylamine (38 mg) in DMF (0.5 ml) was added a solution of 3-methylthiopropylamine (21 mg) in DMF (0.5 ml), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added 2% aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate, and the extract was concentrated by a nitrogen gas blower. The residue was purified by reversed-phase preparative HPLC, and the object fraction was concentrated by a nitrogen gas blower. The residue was dissolved in trifluoroacetic acid/acetonitrile solution (20% (V/V), 1.0 ml), and the mixture was stirred at room temperature for 6 hr. The reaction mixture was concentrated by a nitrogen gas blower. The residue was neutralized with triethylamine (1 ml), saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The extract was concentrated by a nitrogen gas blower. The residue was purified by reversed-phase preparative HPLC, and the object fraction was concentrated by a nitrogen gas blower to give the object compound (6.4 mg).

Provenance & Evidence