Triphenylphosphine → 3-[(1-{3-Cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile

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To a mixture of resin of triphenylphosphine (63.8 mg, 0.133 mmol) and 3-fluoro-5-hydroxybenzonitrile (12.5 mg, 0.0910 mmol) in methylene chloride (0.6 mL) was added di-tert-butyl azodicarboxylate (22.3 mg, 0.0970 mmol) (DBAD). The mixture was stirred for 15 minutes before adding a solution of 4-(3-fluoro-4-hydroxypiperidin-1-yl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (30.3 mg, 0.0606 mmol) (diastereomer 2) in methylene chloride (0.2 mL). The reaction was stirred overnight at room temperature then another portion of resin of triphenylphosphine and DBAD was added and the solution was stirred for 6 hours, then the solvent was evaporated. The vial and resin were washed with DCM and filtered. The filtrates were washed with 10% aq. NaOH. The organic was dried over MgSO4, filtered, and concentrated. The crude was diluted with methanol and purified with preparative LCMS (Sunfire C18 column eluting with a gradient MeCN/H2O containing 0.1% TFA at 30 mL/min) to give the desired product (11 mg, 29%). The product was synthesized from diastereomer 1 using same procedure in 14% yield. LCMS (M+H)+: 619.3.

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