Dimethylformamide → HCID 71667531, compound

Participants

Reaction Steps

In a 40 ml scintillation vial equipped with a magnetic stir bar, the 5-amino-2-chloro-N-[3-(2-oxo-oxazolidin-3-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 15c (73.40 mg, 0.16 mmol) was taken up in clean, dry, reagent-grade N,N-dimethylformamide (3.00 ml, 38.74 mmol) and the reaction mixture was stirred under a nitrogen feed at room temperature until all solids were in solution. To this was then added the HATU (70.90 mg, 0.19 mmol) in one portion followed by the N,N-diisopropylethylamine (0.08 ml, 0.46 mmol) and the reaction mixture was stirred until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (35.70 mg, 0.23 mmol) was added the reaction was allowed to stir at room temperature overnight. The reaction was diluted with 10 ml of water and 10 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, washed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml). The organic solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The product was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 7.5% MeOH in dichloromethane. The product required further purification and was thusly subjected to reverse-phase prep-HPLC, eluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period. The product, 2-cyclopropyl-oxazole-4-carboxylic acid [4-chloro-5-[3-(2-oxo-oxazolidin-3-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 15d (26.60 mg, 0.04 mmol), was isolated as a white solid.

Provenance & Evidence