Preparation of a 990-member chemical compound library of hydantoin- and isoxazoline-containing heterocycles using multipin technology.
The development of a useful chemistry for the construction of polyfunctional heterocycles--first through solution and solid phase (resins) and then library production via SynPhase crowns--is reported. Bead-based synthetic work was done on Merrifield resin where treatment with benzylamine in the presence of DBU followed by reaction with 4-chloromethylbenzoyl chloride afforded amide-linked resin 9. Finally, TFA.NH2-polystyrene macro crowns were derivatized with 4-(hydroxymethyl)benzoic acid to afford pin 14 which was coupled with Boc-protected amino acid 2 in the presence of DIC to deliver pin 15. Deprotection and reaction with phenyl isocyanate afforded urea functionalized pin 17 which underwent 1,3-dipolar cycloaddition reaction to give pin 19. Finally, compound 20 was obtained with moderate diastereoselectivity (20:21::8:1) by the reaction of pin 19 with a catalytic amount of Et3N.
Park
K H
KH
Department of Chemistry, University of California, Davis, California 95616, and Chemical Technologies, Novartis Crop Protection AG, CH-4002 Basel, Switzerland.
Ehrler
J
J
Spoerri
H
H
Kurth
M J
MJ
D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006827:Hydantoins / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007555:Isoxazoles / Q000138:chemical synthesis*; D012116:Resins, Plant; D014508:Urea / Q000737:chemistry
D006571:Heterocyclic Compounds; D006827:Hydantoins; D007202:Indicators and Reagents; D007555:Isoxazoles; D012116:Resins, Plant; D014508:Urea