Solid-phase synthesis of trisubsituted guanidines.
The solid-phase library synthesis of trisubstituted guanidines was accomplished. Amines were loaded onto the 4-formyl-3,5-dimethoxyphenoxymethyl linker via reductive amination. Subsequent acylation with Fmoc-4-aminomethylbenzoic acid followed by Fmoc deprotection gave solid-supported primary amines. Alternatively, sulfonylation of resin-bound secondary amines with 4-cyanobenzenesulfonyl chloride followed by borane reduction also gave solid-supported primary amines. Both resins were acylated with isocyanates to furnish solid-supported ureas. Dehydration of ureas with p-toluenesulfonyl chloride in pyridine gave solid-supported carbodiimides. Nucleophilic addition of amines to the carbodiimide bond followed by cleavage off the solid support gave trisubstituted guanidines.
Hopkins
Thutam P
TP
ChemRx Division, Discovery Partners International, 385 Oyster Point Boulevard, Suite 1, South San Francisco, California 94080, USA.
Dener
Jeffrey M
JM
Boldi
Armen M
AM
D020650:Combinatorial Chemistry Techniques; D006146:Guanidines / Q000138:chemical synthesis*
D006146:Guanidines