Potassium Phosphate, Tribasic → HCID 178482343, compound

Participants

Reaction Conditions

Reaction Steps

(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide (420 mg, 1.17 mmol), 3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (452 mg, 1.75 mmol, 1.5 equiv), tricyclohexylphosphine (49 mg, 0.175 mmol, 0.15 equiv), Pd2(dba)3 (80 mg, 0.088 mmol, 0.075 equiv) and K3PO4 (412 mg, 1.98 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, followed by heating at 100° C. for 20 hours. After cooling to room temperature, the mixture was filtered through celite and rinsed with EtOAc (30 mL). The filtrate was concentrated in vacuo, and the resulting residue was partitioned between EtOAc (30 mL) and brine (10 mL). The organic was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using gradient elution of 1% A in CHCl3 to 70% A in CHCl3 (A was a mixture of 800/80/3200 CH3OH/NH4OH/CHCl3). Trituration of the purified material in a mixture of CHCl3 (1 mL), MTBE (2 mL) and hexane (6 mL), and drying under vacuum at 65° C. for 20 hours afforded the title compound (208 mg) as a tan solid. LC-MS (ES) m/z=456 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.33 (d, J=6.8 Hz, 3H), 1.78-1.96 (m, 3H), 2.05-2.16 (m, 1H), 2.58-2.16 (m, 1H), 2.59 (s, 3H), 2.99 (s, 3H), 3.18-3.27 (m, 1H), 6.53 (s, 1H), 7.12 (t, J=7.3 Hz, 1H), 7.34 (t, J=8.0 Hz, 2H), 7.60 (d, J=7.3 Hz, 2H), 7.68 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 8.04 (s, 1H).

Provenance & Evidence