Hydrochloric Acid → 1-({[6-{4-Chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridin-2-yl]carbonyl}amino)cyclohexanecarboxylic acid hydrochloride

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Reaction Steps

Add, under argon, 0.74 mL (0.41 mmol) of diisopropylethylamine and 409 mg (1.28 mmol) of TBTU to a solution of 200 mg (0.42 mmol) of 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylic acid in 50 mL of anhydrous DMF. In parallel, heat, while stirring under argon, a mixture of 84 mg (0.59 mmol) of 2-aminocyclohexane-2-carboxylic acid and 0.18 mL (0.76 mmol) of N,O-bis(trimethylsilyl)acetamide (BSA) in 5 mL of anhydrous acetonitrile to 90° C. After 2 h, the mixture has dissolved completely. Cool the solution to RT, then add it to the solution of 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridine-2 carboxylic acid activated with TBTU. After stirring for 18 h at RT, add 10 mL of 0.5N HCl aqueous solution and continue stirring for 3 h. Then distribute the reaction mixture in a mixture of 20 mL of EtOAc/ether 1:1 and 10 mL of water. After extraction, extract the aqueous phase again with 10 mL of 1:1 ether/EtOAc mixture. Combine the organic phases, wash with 2×10 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Then purify the residue by reverse-phase HPLC (RP18) eluting with a 0.01N HCl/acetonitrile gradient from 5% to 100% of acetonitrile. After concentration under reduced pressure and tyophilization, we obtain 106 mg of 1-({[6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridin-2-yl]carbonyl}amino)cyclohexanecarboxylic acid hydrochloride in the form of white powder.

Provenance & Evidence