An original traceless linker strategy for solid-phase synthesis of N,N',N''-substituted guanidines.
An original sequence for solution- and solid-phase synthesis of N,N',N"-trisubstituted guanidines is described. The sequence involves as key intermediate a bis-electrophilic chlorothioformamidine that is stable, easy to prepare and also easy to handle. Supported chlorothioformamidine, prepared in two steps from Merrifield resin, undergoes smooth nucleophilic addition of a primary amine to afford the corresponding supported isothiourea. The guanidine is obtained in satisfactory yield and good purity through a functionalizing-release process by heating the supported isothiourea in the presence of a primary amine in toluene at 100 degrees C. Compatibility of this sequence with several functional groups is demonstrated.
Gomez
L
L
Laboratoire de Synthèse Bioorganique, Université Louis Pasteur de Strasbourg, CNRS UMR 7514, Faculté de pharmacie, Illkirch, France.
Gellibert
F
F
Wagner
A
A
Mioskowski
C
C
D002851:Chromatography, High Pressure Liquid; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013890:Thiourea / Q000737:chemistry
D006146:Guanidines; D007202:Indicators and Reagents; D012996:Solutions; D013890:Thiourea