反应详情

The carboxylic acid from Step D (5.14 g, 16.1 mmol), 1-(3-chlorophenyl)piperazin-2-one hydrochloride (3.97 g, 16.1 mmol) (prepared as described in U.S. Pat. No. 5,856,326), EDC hydrochloride (3.70 g, 19.3 mmol), HOBT (2.61 g, 19.3 mmol), and N,N-diisopropylethylamine (14.0 mL, 80.4 mmol) were stirred in dry, degassed DMF (50 mL) at 25° C. for 16 hours. The reaction was poured onto saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a yellow oil. The crude product was purified by column chromatography (3→5% methanol/methylene chloride) and converted to the HCl salt to provide the title compound as a yellow solid.

1. customin dry
2. customdegassed DMF (50 mL) at 25° C. for 16 hours
3. additionThe reaction was poured onto saturated aqueous sodium bicarbonate solution
4. extractionextracted with methylene chloride (3×100 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto provide a yellow oil
10. customThe crude product was purified by column chromatography (3→5% methanol/methylene chloride)