Potassium Phosphate, Tribasic → (3S,6R)-1-[6-(4-Cyano-3,5-difluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

Participants

Reaction Conditions

Reaction Steps

(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (600 mg, 1.64 mmol) and (4-cyano-3,5-difluorophenyl)boronic acid (390 mg, 2.13 mmol, 1.3 equiv), Pd2(dba)3 (113 mg, 0.12 mmol, 0.075 equiv), tricyclohexylphosphine (69 mg, 0.246 mmol, 0.15 equiv), and K3PO4 (592 mg, 2.79 mmol, 1.7 equiv) were charged to a seal tube, followed by addition of 1,4-dioxane (12 mL) and water (4 mL). The mixture was bubbled with argon for 10 minutes, capped and heated at 100° C. for 20 hours. The mixture was filtered through celite, and the filtrate was concentrated in vacuo. The resulting residue was partitioned between EtOAc (50 mL) and brine (15 mL), and the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc afforded the title compound (490 mg). LC-MS (ES) m/z=469 [M+H]+.

Provenance & Evidence