Thionyl Chloride → 5-Chloropyridine-2-carbonyl chloride

Toluene (3.00 ml) was added to 5-chloropyridine-2-carboxylic acid (5.86 mg) to form a suspension. After adding one drop of N,N-dimethylformamide, thionyl chloride (1.00 ml) was added. The reaction mixture was heated to 120° C. stirred at the same temperature for one hour. After cooling to room temperature, the solvent was evaporated under reduced pressure to obtain 5-chloropyridine-2-carboxylic acid chloride. The resulting acid chloride was suspended in tetrahydrofuran (1.00 ml), and the suspension was added dropwise to a solution of the compound 6-4 (10.0 mg) in tetrahydrofuran (2.00 ml) in an ice bath. After adding pyridine (11.3 μl) dropwise at the same temperature, the mixture was warmed to room temperature and stirred for 30 minutes. After confirming completion of the reaction, aqueous sodium bicarbonate was added to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (2.00 ml). Trifluoroacetic acid (0.40 ml) was added and the mixture was stirred at room temperature for three hours. After confirming completion of the reaction, the reaction mixture was diluted with diethyl ether. Aqueous sodium bicarbonate was added to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography to obtain the title compound (7.8 mg).