Solid-phase synthesis of substituted guanidines using a novel acid labile linker.
A novel acid labile linker for solid-phase synthesis of substituted guanidines has been developed. Its synthetic utility is exemplified by high-yielding pyrazole displacement with structurally and electronically diverse sets of aliphatic and aromatic amines. The final cleavage is achieved by treatment with 95:5 trifluoroacetic acid/water for 1 h. The corresponding guanidines were obtained in high purity (80-95%) and good isolated yields (50-95%). The scope and limitations of this linker were further demonstrated by the solid-phase synthesis of an 880-member library of individual trisubstituted arylguanidines employing pyrazole displacement with a set of 11 anilines and two subsequent Mitsunobu N-alkylations with sets of 10 and 8 alcohols, respectively.
Pátek
M
M
Selectide Corporation, a subsidiary of Aventis Pharmaceutical Inc., 1580 East Hanley Boulevard, Tucson, Arizona 85737, USA. marcel.patek@aventis.com
Smrcina
M
M
Nakanishi
E
E
Izawa
H
H
D000588:Amines / Q000737:chemistry*; D015195:Drug Design; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid
D000588:Amines; D006146:Guanidines; D007202:Indicators and Reagents; D011720:Pyrazoles; D014269:Trifluoroacetic Acid