Acetyl chloride → Nalpha-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester.hydrochloride

Participants

Reaction Conditions

Reaction Steps

To 61.67 L of 2-propanol, there was added 5.226 kg of Nα-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-formyl-N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester to thus form a suspension and the resulting suspension was cooled to 10° C. and stirred in a nitrogen gas stream. Acetyl chloride (10.00 kg) was dropwise added to this suspension over one hour while taking care to prevent any excess generation of heat, then 37.67 L of isopropyl acetate was added to the suspension and the resulting mixture was heated with stirring at 70° C. for 24 hours. After the confirmation of the progress of the reaction by HPLC, the slurry was cooled to 25° C. and stirred over 19 hours. The resulting precipitates were recovered by the filtration using a centrifuge and the resulting cake was washed with 20.90 L of 2-propanol. The resulting wet crystals were dried under reduced pressure at 75° C. to thus give 5.159 kg of the title compound as a white crystalline solid (yield: 95%).

Provenance & Evidence