Sodium Carbonate → 5-(piperazin-1-yl)-1H-indole

Bis(2-chloroethyl)amine hydrochloride (3.60 g, 20.2 mmol) was added to a suspension of 5-aminoindole (2.53 g, 19.1 mmol) in ethanol (30 ml) and the mixture heated at reflux for 16 h. The mixture was allowed to cool, sodium carbonate (2.14 g, 20.2 mmol) was added and the reaction mixture heated at reflux for 8 h. The mixture was allowed to cool, filtered and the filtrate evaporated. The residue was dissolved in 1M hydrochloric acid (100 ml) and extracted with dichloromethane (2×50 ml). The aqueous phase was made basic with 4M sodium hydroxide (30 ml) and extracted with ethyl acetate (2×100 ml). The extracts were washed with brine (100 ml), combined and dried (MgSO4). The residue from evaporation of the extracts was purified by flash chromatography, eluting with dichloromethane/methanol/ammonia, to give 1-(5-indolyl)piperazine (0.71 g, 18%), as a cream solid; δH (DMSO-d6) 2.94 (4H, m, 2×piperazinyl CH2), 3.00 (4H, m, 2×piperazinyl CH2), 6.29 (1H, m, 3-H), 6.84 (1H, dd, J 9.0, 2.0 Hz, 6-H), 7.00 (1H, d, J 2.0 Hz, 2-H), 7.24 (2H, m, 4-H, 7-H), and 10.82 (1H, br s, NH).

1. temperaturethe mixture heated
2. temperatureat reflux for 16 h
3. temperatureto cool
4. temperaturethe reaction mixture heated
5. temperatureat reflux for 8 h
6. temperatureto cool
7. filtrationfiltered
8. customthe filtrate evaporated
9. dissolutionThe residue was dissolved in 1M hydrochloric acid (100 ml)
10. extractionextracted with dichloromethane (2×50 ml)
11. extractionextracted with ethyl acetate (2×100 ml)
12. washThe extracts were washed with brine (100 ml)
13. dry with materialdried (MgSO4)
14. customThe residue from evaporation of the extracts
15. customwas purified by flash chromatography
16. washeluting with dichloromethane/methanol/ammonia

ORD-Eintrag

ord-a16e7b7768494aeb81a9138676a50b88

Quelldatensatz

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05622950