Sodium Bicarbonate → 4-Amino-6-chloro-5-cyano-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamide

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Reaction Steps

4-Amino-6-chloro-5-cyanopicolinic acid (1.053 g, prepared according to the reported preparation in Zhao, Hongyu, et al.; J. Med. Chem. 2006, 49(15), 4455-4458), the compound prepared in Example 214 (2.12 g), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (3.33 g) and triethylamine (7.43 mL) were suspended in N,N-dimethylformamide (100 mL) and stirred at room temperature over weekend. The reaction mixture was poured onto saturated aqueous sodium bicarbonate solution and ethyl acetate. The organics were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford the crude material. The crude material was slurried with dichloromethane and the desired material precipitated out of solution. The solids was filtered and washed with dichloromethane to afford clean material. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (gradient elution: 100% ethyl acetate to 96.5% ethyl acetate, 2.5% triethylamine 1% methanol) to afford pure material, which was combined with the triturated material to give the title compound (1.69 g), with the following physical data.

Provenance & Evidence