Pyridine → HCID 178487899, compound

Participants

Reaction Steps

6-Methoxyquinoline-3-carboxylic acid was prepared from p-anisidine using the methods of Erickson (J. Med. Chem., 1979, 22, 7, 816–823). A solution of 6-methoxyquinoline-3-carboxylic acid hydrochloride (500 mg, 2.09 mmol) in thionyl chloride (25 mL) was heated at reflux for 1 hour. After this time the excess thionyl chloride was removed by distillation and the remaining solid dried under vacuum. The solid was suspended in dichloromethane (25 mL) and treated with trans-4-methylcyclohexylamine hydrochloride (368 mg, 2.46 mmol), pyridine (5 mL), and triethylamine (0.345 mL). The reaction was stirred at ambient temperature overnight. After this time the reaction mixture was diluted with diethyl ether (200 mL) and the resulting organic solution washed with 1 N NaOH (3×50 mL) and then brine (1×). The organic solution was then dried over anhydrous MgSO4, filtered, and concentrated to a solid. Chromatography of the crude product through a Biotage silica cartridge (8×4 cm i.d.) using a gradient of hexane to 50% ethyl acetate (in hexane) afforded 100 mg (16%) of 419:

Provenance & Evidence