反应详情

(R)-2-[2-(2-Hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 5d (2.1 g, 6.2 mmol) and lithium hydroxide monohydrate (1.56 g, 37 mmol) were dissolved in 25 mL of glycol under stirring under an argon atmosphere. The reaction system was stirred at 140° C. in an oil bath for 50 minutes. The reaction was completed until TLC showed the disappearance of starting materials. After thin lay chromatography showed the starting material disappeared, the solvent was evaporated under reduced pressure, and 50 mL of saturated brine was then added to the residue. The mixture was extracted with dichloromethane (80 mL×3). The combined organic extracts were washed with saturated brine (80 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 5e (610 g, yield 33.9%) as a white solid.

1. stirringThe reaction system was stirred at 140° C. in an oil bath for 50 minutes
2. customthe solvent was evaporated under reduced pressure, and 50 mL of saturated brine
3. additionwas then added to the residue
4. extractionThe mixture was extracted with dichloromethane (80 mL×3)
5. washThe combined organic extracts were washed with saturated brine (80 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. customto remove the drying agent
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography