Lithium Hydroxide → N-{5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-fluorophenyl}-2,6-difluorobenzamide

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Reaction Steps

A solution of N-{5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-fluorophenyl}-2,2,2-trifluoroacetamide (300 mg, 0.69 mmol) and 1M LiOH (4.13 ml, 4.13 mmol) in 10:1 THF:H2O (15 mL) was heated at 50° C. overnight. The reaction was washed with brine (25 mL) and the aqueous layer was extracted with EtOAc (25 mL). The organic layers were combined, filtered through a cotton plug, and solvent removed by rotary evaporation. After high vacuum removal of residual solvent, the crude mixture was dissolved in DCM (10 mL) and to this was added 2,6-difluorobenzoyl chloride (519 mg, 2.94 mmol). After stirring 3 h at ambient temperature, DMF (25 mL) was added to dissolve any suspended solids followed by the addition of excess polymer-bound trisamine resin. Upon overnight stirring, the amine resin was removed by vacuum filtration, rinsed with MeOH (50 mL), and filtrate concentrated under reduced pressure to afford the desired amide (162 mg, 49%) as an off-white solid. ESIMS (M+H)+=480.

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