Hydrochloric Acid → MLN4924 hydrochloride

Participants

Reaction Conditions

Reaction Steps

A flask was charged with ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate (25 g, 56.4 mmol) and 200-proof ethanol (300 mL). The mixture was heated to 70-75° C. to afford a clear solution. The mixture was cooled to 50±5° C. 1.25M hydrogen chloride in ethanol (25 mL, 31 mmol) was added rapidly at a rate to maintain a temperature of 50±5° C. The mixture was then seeded with Form 1. Further 1.25M HCl (25 mL, 31 mmol) was added over a period of about 60 minutes, maintaining a temperature of 50±5° C. The mixture was then stirred at 50±5° C. for about 2 hours. The mixture was then cooled to 20±5° C. over about 2 hours and then stirred for about 17 hours. The solid product was then isolated by filtration and washed with 200-proof ethanol (50 mL). The solids were dried by aspiration on the filter for about 5 hours, and then further dried under reduced pressure at 30-35° C. to afford the title compound (22.5 g) as a white solid.

Provenance & Evidence