Toluene → (R)-(3-methyl-4-(4-p-tolylphthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

Participants

Reaction Conditions

Reaction Steps

Compound 20 was prepared as described generally in synthetic Method D. Substrate JK-5 was prepared as described in detail in Example 11. To a reaction flask was added (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone (JK-5) (200 mg, 0.54 mmol), p-tolyl boronic acid (111 mg, 0.82 mmol, 1.5 eq), and Pd(PPh3)4 (31 mg, 0.027 mmol, 0.05 eq). The flask was fitted with a reflux condenser and purged with nitrogen. Toluene (5.4 mL) and aqueous Na2CO3 (2 M, 0.54 mL, 2 eq) were added and the reaction was heated to 100° C. overnight. The reaction was then cooled to rt and diluted with 75 mL of ethyl acetate. The organic phase was washed with 1×10 mL of sat. NaHCO3 solution, 1×10 mL of H2O, and 1×10 mL of sat. NaCl solution. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography (60% ethyl acetate in hexanes) afforded 197 mg (86%) of (R)-(3-methyl-4-(4-p-tolylphthalazin-1-yl)piperazin-1-yl)(phenyl)methanone 20 MS (M+H)+=423.3.

Provenance & Evidence