Dimethylformamide → (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde

Participants

Reaction Steps

Phosphorus oxychloride (500 μL, 1.3 mmol) and N,N-dimethylformamide (704 μL, 9 mmol) were dissolved in 15 mL of anhydrous dichloromethane under stirring at room temperature, and the reaction solution was stirring for 15 minutes while maintaining the temperature at −10° C. in an ice-water bath. (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 5e (586 mg, 2 mmol) was dissolved in 8 mL of dichloromethane under stirring, and the solution was then added dropwise to the above reaction system. Upon completion of the addition, the ice-water bath was removed. The reaction system was allowed to warm up to room temperature and stirred for another 2 hours. The reaction was completed until TLC showed the disappearance of starting materials. The reaction mixture was quenched with iced water and stirred for 15 minutes. The mixture was adjusted to pH about 12 with 10N sodium hydroxide solution. The mixture was extracted with the solvent mixture of dichloromethane and methanol (V:V=20:1, 100 mL ×5). The combined organic extracts were washed with saturated brine (100 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-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde 5f (490 mg, yield 78.8%) as a white solid.

Provenance & Evidence