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

Participants

Reaction Conditions

Reaction Steps

(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (500 mg, 1.34 mmol) and (4-cyano-3,5-difluorophenyl)boronic acid (318 mg, 1.74 mmol, 1.3 equiv), Pd2(dba)3 (92 mg, 0.10 mmol, 0.075 equiv), tricyclohexylphosphine (56 mg, 0.20 mmol, 0.15 equiv), and K3PO4 (483 mg, 2.27 mmol, 1.7 equiv) were charged to a 30 mL microwave vial, followed by addition of 1,4-dioxane (10 mL) and water (3.3 mL). The mixture was bubbled with argon for 10 minutes, and heated at 100° C. for 20 hours. After cooling to room temperature, 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 (470 mg) as a yellow/greenish gum. LC-MS (ES) m/z=477 [M+H]+.

Provenance & Evidence