Potassium Phosphate, Tribasic → HCID 178482345, compound

Participants

Reaction Conditions

Reaction Steps

(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (370 mg, 0.99 mmol), 3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (383 mg, 1.48 mmol, 1.5 equiv), tricyclohexylphosphine (42 mg, 0.5 mmol, 0.15 equiv), Pd2(dba)3 (68 mg, 0.07 mmol, 0.075 equiv) and K3PO4 (357 mg, 1.68 mmol, 1.7 equiv) were charged to a 30 mL microwave vial, followed by addition of 1,4-dioxane (4 mL) and water (1.33 mL). The mixture was bubbled with argon for 10 minutes, followed by capping and heating at 100° C. for 20 hours. This mixture was combined with another run starting with 200 mg of (3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide. The combined mixture was filtered through celite, and rinsed with EtOAc (50 mL). The filtrate was concentrated in vacuo, and the resulting residue was partitioned between EtOAc (75 mL) and brine (20 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 50% A in CHCl3 (where A was a mixture of 800/80/3200 CH3OH/NH4OH/CHCl3). Trituration of the purified material in a mixture of CHCl3 (1 mL) and hexane (6 mL), and drying under vacuum at 65° C. afforded the title compound (312 mg) as a tan solid. LC-MS (ES) m/z=470 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.30 (d, J=6.8 Hz, 3H), 1.75-1.90 (m, 3H), 1.97-2.10 (m, 1H), 2.42-2.54 (m, 1H), 2.59 (s, 3H), 2.97 (s, 3H), 3.10-3.20 (m, 1H), 4.42 (s, 2H), 4.60-4.70 (bs, 1H), 4.75-4.85 (bs, 1H), 6.49 (s, 1H), 7.25-7.37 (m, 5H), 7.65 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.3 Hz, 1H), 8.02 (s, 1H).

Provenance & Evidence