Diisopropylethylamine → N-[(1R*,2S*)-2-Aminocyclopropyl]-5-chloroindole-2-carboxamide

1-Hydroxybenzotriazole monohydrate (377 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (642 mg) and diisopropylethylamine (1.95 ml) were added to cis-1,2-cyclopropanediamine hydrochloride (J. Med. Chem., 1998, Vol. 41, pp. 4723-4732) (405 mg) and a solution of 5-chloroindole-2-carboxylic acid (546 mg) in N,N-dimethylformamide (10 ml) at room temperature, and the mixture was stirred for 50 hours. After the reaction mixture was concentrated under reduced pressure, dichloromethane (50 ml) and a saturated solution (200 ml) of sodium hydrogencarbonate were added to separate colorless solid deposited by filtration. An organic layer of the filtrate was separated and the water layer was extracted with dichloromethane. After the resultant organic layers were combined and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain residue. The residue was purified by medium-pressure flash column chromatography on silica gel (dichloromethane:methanol=100:7→10:1) to obtain the title compound (110 mg) as a colorless solid.

1. concentrationAfter the reaction mixture was concentrated under reduced pressure, dichloromethane (50 ml)
2. additiona saturated solution (200 ml) of sodium hydrogencarbonate were added
3. customto separate colorless solid
4. filtrationdeposited by filtration
5. customAn organic layer of the filtrate was separated
6. extractionthe water layer was extracted with dichloromethane
7. dry with materialdried over anhydrous sodium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customto obtain residue
10. customThe residue was purified by medium-pressure flash column chromatography on silica gel (dichloromethane:methanol=100:7→10:1)

ORD record

ord-3d5cf34238d84ec690f749d301c1d27c

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07192968B2