Ethyl 4-piperidinecarboxylate → HCID 86648396, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,5-bis(trifluoromethyl)benzyl-[(3S,5R)-1-(2,5-dichloro-pyrimidin-4-yl)-5-ethyl-pyrrolidin-3-yl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (50.6 mg, 0.0784 mmol), ethyl isonipecotate (31 μL, 0.196 mmol) and diisopropyl-ethylamine (21 μL, 0.118 mmol) in sec-butanol (2 mL) is stirred at 120° C. for 10 hour. After addition of ethyl isonipecotate (12 μL, 0.0784 mmol) and diisopropyl-ethylamine (27 μL, 0.157 mmol), the mixture is stirred for additional 8 hours. The mixture is diluted with dichloromethane and washed with waterm 1N HCl aq, and the brine, dried over sodium sulfate and concentrated in vacuo. The obtained residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:2 to 5% MeOH in AcOEt) to give (1-[5-chloro-4-((2R,4S)-4-{[3,5-bis(trifluoromethyl)-benzyl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-pyrimidin-2-yl]-piperidine-4-carboxylic acid ethyl ester, 34.7 mg). The obtained solid is dissolved in MeOH (2.5 mL), 1N NaOH aq (225 μL, 0.225 mmol) and water (0.3 mL), and the resulting mixture was stirred at room temperature for 18 hour. 1N HCl (225 μL, 0.225 mmol) and then MeOH were added to the mixture and the solvent was removed by evaporation. The residue was dissolved in dichloromethane and then filtered. The filtrate was evaporated to give 1-[5-chloro-4-((2R,4S)-4-{[3,5-bis(trifluoromethyl)-benzyl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-pyrimidin-2-yl]-piperidine-4-carboxylic acid (29.2 mg, 51%).

Provenance & Evidence