Reaction #489236

Reaction equation

6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester hydrochloride

6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (morpholin-2-ylmethyl)-amide dihydrochloride

8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylamine

ethyl-diisopropyl-amine

→

title compound

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

Solvents

THF

diethyl ether

Conditions

Workup

1. 1
   Washwashed with water and 2 M aq. sodium hydroxide solution
2. 2
   Dryingdried over magnesium sulfate
3. 3
   OtherThe crude product may be purified by column chromatography on silica gel using 2-5% 2 M ammonia in MeOH in DCM
4. 4
   workup.ADDITIONtreated with 4 N HCl in dioxane
5. 5
   OtherThe organic solvents may be removed under reduced pressure
6. 6
   Otherthe product dried overnight under high vacuum

Procedure

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).

Source