An efficient sequence for the preparation of small secondary amine hydrochloride salts for focused library generation without need for distillation or chromatographic purification.
Collections of small secondary amines for compound library generation can be efficiently prepared by amide reduction using BH(3)-THF or Red-Al followed by brief methanolysis, trapping with di-tert-butyl dicarbonate, and deprotection with 4M HCl in dioxane. The sequence requires no chromatography or distillation and provides multi-gram quantities of pure HCl salts in a short time.
Dubowchik
Gene M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5100, Wallingford, CT 06492-7660, USA. gene.dubowchik@bms.com
Michne
Jodi A
JA
Zuev
Dmitry
D
D000588:Amines / Q000032:analysis / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002849:Chromatography, Gas / Q000379:methods; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D019151:Peptide Library; D012492:Salts / Q000032:analysis / Q000138:chemical synthesis*
D000588:Amines; D019151:Peptide Library; D012492:Salts