Methanesulfonic Acid → Pranlukast Chromene Carboxamide Impurity

Participants

Reaction Conditions

Reaction Steps

To a mixture containing 120 ml of 5-ethyl-2-methylpyridine and 75 ml of methanol was added 29.5 g of 8-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-ethoxycarbonyl-4-oxo-4H-benzopyran, into which 8.2 g of ammonia gas was bubbled around 0° C., and the mixture was stirred below 30° C. for 3 hours. Then, the temperature was increased to 80° C., and excess ammonia and part of the methanol were removed and recovered into methanol in another vessel. The recovered ammonia and/or methanol can be used again in the subsequent production. The temperature was increased to 80° C., and the remaining methanol and part of 5-ethyl-2-methylpyridine were removed by reducing a pressure down to 30 mmHg. Subsequently, 60.8 mmol (5.84 g) of methane sulfonic acid was added, and the mixture was stirred at 100° C. for 6 hours. Then, the temperature was decreased to 60° C., and methanol was added dropwise at 50° to 60° C. The mixture Was cooled to 0° C., and the deposited crystals were collected by filtration, which afforded 27.7 g of 8-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-carbamoyl-4-oxo-4H-benzopyran (yield 99%).

Provenance & Evidence