Trifluoroacetic acid → 3-Benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine

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Reaction Steps

To 4-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (170 mg, 0.358 mmol) is added 50% TFA in DCM. The reaction mixture is stirred for 10 min and concentrated to afford 3-benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine as a yellow sticky solid (125 mg, 100%). To a solution of 3-benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine (180 mg, 0.644 mmol) in dioxane is added methyl-5-chloropyrazine-2-carboxylate (222 mg, 1.29 mmol) and TEA (0.45 mL, 3.22 mmol) in a microwave tube. The reaction mixture is heated at 160° C. for 40 min in a microwave reactor. The mixture is concentrated to afford a brown oil and purified by prep HPLC, eluting with 10%-100% acetonitrile:water (both mobile phases modified by 3% n-PrOH). Fractions containing the desired product are combined and freeze-dried to afford a white solid (80 mg, 30%).

Provenance & Evidence