Nitrogen → 1-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidin-4-ol

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Reaction Steps

A 25 ml round-bottom flask is charged with 1-(tetrahydro-pyran-2-yl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (56 mg, 0.2 mmol), 1-(4-{(2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidin-1-yl}-5-chloro-pyrimidin-2-yl)-piperidin-4-ol (110 mg, 0.15 mmol) under N2. Pd(PPh3)4 (34 mg, 0.03 mmol) is added promptly and the flask is recharged with N2. Then DME (0.5 ml), Na2CO3 (1 M in H2O, 0.3 ml, 0.3 mmol) are added. The mixture is then heated to 95 degree for 2 hours. After cooling down to rt, NaIO4 (103 mg, 0.48 mmol) is added into reaction mixture. Stirring is continued for 1 h to give white suspension. H2O and dichloromethane are added, then organic layer is collected with phase separator. Removal of solvent gave 1-{4-[(2R,4S)-4-((3,5-bis-trifluoromethyl-benzyl)-{5-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-amino)-2-ethyl-pyrrolidin-1-yl]-5-chloro-pyrimidin-2-yl}-piperidin-4-ol which is used without further purification.

Provenance & Evidence