1,4-Dioxane → (3S,6R)-1-[6-(4-Cyano-3-fluorophenyl)-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 (300 mg, 0.80 mmol), (4-cyano-3-fluorophenyl)boronic acid (176 mg, 1.07 mmol, 1.3 equiv), Pd2(dba)3 (56 mg, 0.061 mmol, 0.075 equiv), tricyclohexylphosphine (34.5 mg, 0.123 mmol, 0.15 equiv), and K3PO4 (296 mg, 1.39 mmol, 1.7 equiv) were charged to a 30 mL microwave vial, followed by addition of 1,4-dioxane (6 mL) and water (2 mL). The mixture was bubbled with argon for 10 minutes, and heated at 100° C. for 20 hours. A duplicate run was performed. The crude mixture of both runs were combined and filtered through celite, and the filtrate was concentrated in vacuo. The residue was partitioned between EtOAc (50 mL) and brine (15 mL). The organic was dried over Na2SO4, filtered and conc in vacuo. Purification by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc gave the title compound (636 mg) as a foam. LC-MS (ES) m/z=459 [M+H]+.

Provenance & Evidence