Dimethylformamide → HCID 89692967, 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-N-(3-dimethylaminomethyl-benzyl)-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-benzamide 13b (142.50 mg, 0.28 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 nitrogen until all solids were in solution. To this stirred solution was added the HATU (159.70 mg, 0.42 mmol) followed by the N,N-diisopropylethylamine (0.15 ml, 0.86 mmol) and the mixture was again stirred at room temperature until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (55.70 mg, 0.36 mmol) was added to the mixture and the reaction was allowed to stir over night at room temperature. The reaction 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 using ethyl acetate (3×20 ml). The organic phases were combined and the solution was washed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml). The solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The resultant brown oil was then purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 90% dichloromethane/9% MeOH/1% NH4OH. The desired product, 2-cyclopropyl-oxazole-4-carboxylic acid {4-chloro-5-(3-dimethylaminomethyl-benzylcarbamoyl)-2-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-phenyl}-amide 13c (33.60 mg, 0.05 mmol), was isolated as a white solid.

Provenance & Evidence