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; 97.2 g), is charged with 3-amino-1-morpholin-4-yl-propan-1-one, compound with phenylacetic acid (765 mmol) and 2-[2-(4-fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic acid phenylamide (450 mmol). THF (360 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. Half-saturated aqueous NaHCO3 (100 mL) is added, 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 solid is washed with distilled water (100 mL) and MtBE (2×100 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 (194 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. additionHalf-saturated aqueous NaHCO3 (100 mL) is added
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 solid is washed with distilled water (100 mL) and MtBE (2×100 mL)
12. customcollected
13. customdried under vacuum at ≦50° C.