Dimethylformamide → (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole

1,2-dimethylindole-3-carboxylic acid (1.05 g, 5.5 mmol) was dissolved with oxalyl chloride (0.55 ml, 6 mmol) and dimethylformamide (0.1 ml) in dichloromethane (30 ml) and stirred at room temperature for one hour. The mixture was then concentrated under reduced pressure, and the residue was dissolved in dichloromethane (20 ml). The resulting mixture was added dropwise at 0° C. to a solution of (S)-3-amino-1-azabicyclo[2.2.2]octane (0.7 g, 5.5 mmol) in dichloromethane (10 ml). The solution was stirred at room temperature for 30 minutes, after which the solvent was removed under vacuum. The residue was dissolved in water and washed with ethyl acetate. The aqueous layer was made basic with 10N aqueous sodium hydroxide, filtered and extracted with ethyl acetate. The organic layer was dried with anhydrous potassium carbonate, filtered, and then evaporated. Recrystallization from ethyl acetate afforded 0.7 g (46% yield) (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole, m.p. 176°-177° C.; [α]D25 -51.90 (c 0.92, CHCl3). Anal. for C18H23N3O: Calcd: C, 72.70; H, 7.79; N, 14.13. Found: C, 72.75; H, 7.89; N, 14.15.

1. concentrationThe mixture was then concentrated under reduced pressure
2. dissolutionthe residue was dissolved in dichloromethane (20 ml)
3. stirringThe solution was stirred at room temperature for 30 minutes
4. customafter which the solvent was removed under vacuum
5. dissolutionThe residue was dissolved in water
6. washwashed with ethyl acetate
7. filtrationfiltered
8. extractionextracted with ethyl acetate
9. dry with materialThe organic layer was dried with anhydrous potassium carbonate
10. filtrationfiltered
11. customevaporated
12. customRecrystallization from ethyl acetate

ORD record

ord-39b293351cc0478ab78c887d84b8e774

Source dataset

uspto-grants-1993_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05189041