L-Lactic Acid → HCID 178462375, compound

Participants

Reaction Conditions

Reaction Steps

1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea (1.0 wt), in a Class 2 or Class 3 solvent, in particular a Class 3 solvent such as aqueous ethanol (5.0-10.0 vol), can be charged to a flange flask equipped with a mechanical stirrer and thermometer. The contents are stirred under an inert atmosphere e.g. nitrogen and L-lactic acid (0.269 wt) can be added at 15 to 25° C. followed by a line rinse of the appropriate solvent such as aqueous ethanol (0.5 vol). The mixture can be stirred at 15 to 25° C. for 120 to 140 minutes. The solid may be isolated by filtration or by use of addition of anti-solvent such as n-butanol to bring the salt out of solution and then isolated by filtration. The filter-cake can be washed with the appropriate solvent (2×1.0 vol) and pulled dry for 20 to 40 minutes. The filter-cake can then be dissolved in a Class 2 or Class 3 solvent, or mixture thereof, in particular a Class 3 solvent (˜3-60 vol) at 40 to 150° C., cooled to 40 to 70° C. and the solution clarified through glass microfibre paper. The filtrates can be cooled to and aged at 15 to 25° C. for 2 to 3 hours. The crystallised solid can be isolated by filtration, the filter-cake washed with the appropriate solvent (2×0.5-2 vol) and pulled dry for at least 30 minutes. The solid can then be dried under vacuum at 35 to 45° C. to yield 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea L-lactic acid salt. In addition, alternative methods of purification aside from recrystallisation may be employed for purification of the product such as flash column chromatography or filtration through a plug of silica gel or reverse-phase silica gel.

Provenance & Evidence