Use of quinolinium salts in parallel synthesis for the preparation of 4-amino-2-alkyl-1,2,3,4-tetrahydroquinoline.
Compounds of pharmacological interest containing a 4-amino-2-alkyl-1,2,3,4-tetrahydroquinoline core structure were prepared starting from 4-chloroquinoline. This has been executed both in solution with a 1-benzyl-4-chloroquinolinium salt and on a solid support with a 1-(4-benzyloxybenzyl-PS)-4-chloroquinolinium resin as key intermediates. Diversification of such intermediates was accomplished through N-arylation of position 4 and subsequent nucleophilic addition of Grignard reagents of position 2 to deliver the expected 4-amino-2-alkyl-1,2,3,4-tetrahydroquinolines in 20-60% yields. The methods described within clearly demonstrate that the quinolinium salts are very efficient intermediates for parallel synthesis.
Bazin
Marc
M
Department of Chemistry, Pfizer Global Research & Development, Research Technology Center, 620 Memorial Drive, Cambridge, Massachusetts 02139, USA.
Kuhn
Cyrille
C
D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D013058:Mass Spectrometry; D015394:Molecular Structure; D011806:Quinolinium Compounds / Q000737:chemistry*
D011806:Quinolinium Compounds