Hydrochloric Acid → Cinnoline-6-carboxylic acid 3-phenoxy-benzylamide

Participants

Reaction Steps

To a solution of cinnoline-6-carboxylic acid methyl ester described in Preparation Example F-4 (16 mg, 0.085 mmol) in ethanol (1 mL) was added an aqueous solution of 1N sodium hydroxide (0.7 mL), and the solution was stirred at room temperature for 2 hours. 1N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, toluene was added, and the solution was concentrated in vacuo. To a solution of the obtained residue in N,N-dimethylformamide (2 mL) were added 4-phenoxybenzylamine described in Preparation Example 3 (17 mg, 0.085 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (48 mg, 0.108 mmol) and triethylamine (24 μl, 0.172 mmol), and the solution was stirred at room temperature for 14 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate, the organic layer was washed with an aqueous solution of saturated sodium bicarbonate, and then concentrated. The residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used), and the title compound (4.4 mg, 0.0093 mmol, 11%) was obtained as a trifluoroacetic acid salt.

Provenance & Evidence