Water → (S)-3-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-3-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester (2.2 mmol, 1.28 g), 1-methylpyrazol-3-yl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.7 mmol, 0.72 g), tetrakis(triphenylphosphine)palladium(0) (0.22 mmol, 260 mg) and 2M aqueous sodium hydrogen carbonate (3.2 mL) in 1,2-dimethoxy-ethane (15 mL) is allowed to warm to 95° C. and stirred for 3 hours. The mixture is cooled to room temperature and then added water. The mixture is extracted with CH2Cl2. The combined organic layer is dried over Na2SO4, filtrated, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (S)-3-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester 766 mg, 61%). ESI-MS m/z: 571 [M+1]+, Retention time 2.25 min (condition A).

Provenance & Evidence