反应详情

Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridine-2-carboxylate (136 mg), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (255 mg) and 1-hydroxybenzotriazole monohydrate (90 mg) were added to a solution with (±)-cis-N-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclobutanediamine (117 mg) dissolved in N,N-dimethylformamide (5 ml), and the mixture was stirred overnight at room temperature. The solvent was then distilled off under reduced pressure using a vacuum pump, and dichloromethane and a saturated aqueous solution of sodium hydrogencarbonate were added to the residue to conduct liquid separation. The resultant organic layer was washed with saturated saline and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography on silica gel (methanol:dichloromethane=7:93). After ethyl acetate and a 1N ethanol solution of hydrochloric acid were added to the thus-obtained compound to acidify it, and the solvent was distilled off under reduced pressure. Ethyl acetate was added again, and precipitate formed was collected by filtration and dried to obtain the title compound (56 mg) as a colorless powder.

1. distillationThe solvent was then distilled off under reduced pressure
2. additiona saturated aqueous solution of sodium hydrogencarbonate were added to the residue
3. customliquid separation
4. washThe resultant organic layer was washed with saturated saline
5. dry with materialdried over anhydrous sodium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. customthe residue was purified by flash column chromatography on silica gel (methanol:dichloromethane=7:93)
8. additionAfter ethyl acetate and a 1N ethanol solution of hydrochloric acid were added to the thus-obtained compound
9. distillationthe solvent was distilled off under reduced pressure
10. additionEthyl acetate was added again
11. customprecipitate formed
12. filtrationwas collected by filtration
13. customdried