反应详情

A nitrogen inerted reactor, equipped with a suitable reflux condenser and soxhlet extractor containing freshly activated 3A molecular sieves (4-8 mesh; 36 g), is charged with 3-amino-1-morpholin-4-yl-propan-1-one hydrochloride (170 mmol), phenylacetic acid sodium salt (170 mmol) and 2-[2-(4-fluorophenyl)-2-oxo-1-phenyl-ethyl]4-methyl-3-oxo-pentanoic acid phenylamide (100 mmol). THF (150 mL) is added, and the resulting solution is stirred vigorously as the reaction is heated at reflux temperature for ca. 24 hours, during which time the product begins to precipitate. Aqueous NaHCO3 (100 mL) is added slowly, and the reaction mixture is cooled with continued stirring to ca. 0° C. MtBE (100 mL) is added, and the solids are collected via filtration. The yellow-colored solid is washed with distilled water (15 mL) and MtBE (2×15 mL), collected, and dried under vacuum at ≦50° C. to afford 5-(4-fluorophenyl)-2-isopropyl-1-(3-morpholin-4-yl-3-oxo-propyl)-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide as a white solid (42.1 g). This material is carried on to subsequent steps without further purification.

1. customA nitrogen inerted reactor, equipped with a suitable reflux condenser
2. additionsoxhlet extractor containing freshly
3. temperatureis heated
4. temperatureat reflux temperature for ca. 24 hours
5. customto precipitate
6. additionAqueous NaHCO3 (100 mL) is added slowly
7. temperaturethe reaction mixture is cooled
8. stirringwith continued stirring to ca. 0° C
9. additionMtBE (100 mL) is added
10. filtrationthe solids are collected via filtration
11. washThe yellow-colored solid is washed with distilled water (15 mL) and MtBE (2×15 mL)
12. customcollected
13. customdried under vacuum at ≦50° C.