Dimethylformamide → HCID 89692822, compound

Participants

Reaction Steps

In a 40 ml scintillation vial equipped with a magnetic stir bar and fitted with a nitrogen inlet, the 5-amino-2-chloro-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 12d (158.70 mg, 0.33 mmol) was taken up in clean, dry N,N-dimethylformamide (3.00 ml, 38.74 mmol) and the mixture was stirred at room temperature under an inert nitrogen atmosphere until all solids were taken up in solution. To this mixture was then added the HATU (188.20 mg, 0.49 mmol) followed by the N,N-diisopropylethylamine (0.17 ml, 0.98 mmol) and the mixture was again stirred until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (65.70 mg, 0.43 mmol) was then added to the reaction mixture and the reaction was allowed to stir under nitrogen at room temperature overnight. The reaction mixture was diluted with 15 ml of water and 15 ml of ethyl acetate. The layers were separated and the product was extracted from the aqueous solution using ethyl acetate (3×20 ml) and the organic phases were combined, washed with brine (1×25 ml) and saturated aqueous lithium chloride solution (2×25 ml). The solution was dried over Na2SO4; the product solution was decanted and the solvent was removed under reduced pressure. The resultant brown semi-solid was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. The product, 2-cyclopropyl-oxazole-4-carboxylic acid {4-chloro-2-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-phenyl}-amide 12e (81.80 mg, 0.13 mmol), was isolated as an off-white solid and was submitted for testing.

Provenance & Evidence