Diisopropylethylamine → 6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide dihydrochloride

Participants

Reaction Steps

A mixture of 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester hydrochloride (Example 90, 0.108 mmol, 60 mg), 8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylamine (0.05 mL), ethyl-diisopropyl-amine (0.2 mL) in THF (2.0 mL) may be stirred at room temperature for 3 h. The reaction mixture may be diluted with diethyl ether, washed with water and 2 M aq. sodium hydroxide solution and dried over magnesium sulfate. The crude product may be purified by column chromatography on silica gel using 2-5% 2 M ammonia in MeOH in DCM and treated with 4 N HCl in dioxane. The organic solvents may be removed under reduced pressure, and the product dried overnight under high vacuum to provide the free base of the title compound. 1H NMR (free base, 400 MHz, CDCl3) δ 8.72 (1H, d), 8.09 (1H, s), 7.27 (2H, d), 7.01 (2H, d), 4.30-4.36 (2H, m), 3.20 (2H, bs), 3.08 (2H, t), 2.32 (3H, s), 1.26-2.35 (22H, m), 0.87 (3H, t).

Provenance & Evidence