Methyl Acetate → 3-(2-Allyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-n-cyclopropyl-4-methyl-benzamide

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Reaction Steps

Sodium hydride (75 mg, 60% in oil) was added to a stirred mixture of 4-methyl-3-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzoic acid, methyl ester (Intermediate 3) (250 mg), methyl acetate (0.5 mL) and DMF (5 mL). The mixture was stirred for 15 minutes. Allyl bromide (0.5 mL) was added via syringe and the mixture was stirred for 30 minutes, then quenched with sat. aqueous NH4Cl solution and extracted into ethyl acetate. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give crude ester. The ester was treated with THF (5 mL) and cyclopropylamine (0.3 mL). A solution of isopropylmagnesium chloride (2M, 0.4 mL) in THF was added dropwise. The reaction mixture was stirred for 10 minutes, quenched with sat. aqueous NH4Cl solution and extracted into ethyl acetate. The phases were separated, the organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give crude product (380 mg). A sample (80 mg) of crude product was purified by HPLC to give an analytical sample of the title compound as a solid (45 mg).

Provenance & Evidence