Hydrochloric Acid → HCID 59614403, compound

Participants

Reaction Steps

A 5 ml test tube for microwave reactor is charged with ethyl piperidine 4-carboxylate (202 mg, 1.28 mmol), (3,5-bis-trifluoromethyl-benzyl)-[(3S,5S)-1-(2,5-dichloro-pyrimidin-4-yl)-5-methoxymethyl-pyrrolidin-3-yl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (170 mg, 0.26 mmol) and isopropanol (1.5 ml). Then, the test tube is set into microwave reactor at 95 degree for 2 hours. After cooling to rt, reaction mixture is transferred into a 25 ml round-bottom flask and solvent is removed under reduced pressure. Then, into the flask is added 1N NaOH (1.28 ml, 1.28 mmol). The mixture is stirred for 1 hour, and pH is adjusted to 6-7 using 1.5 N HCl. The resulted solution is extracted with EtOAc and the organic layer is dried over MgSO4. The solvent is removed under reduced pressure, and the obtained residue is purified with reverse phase column to give 1-[4-((2S,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-methoxymethyl-pyrrolidin-1-yl)-5-chloro-pyrimidin-2-yl]-piperidine-4-carboxylic acid (78 mg, 0.74 mmol, 58% for 2 steps).

Provenance & Evidence