Efficient synthesis of trisubstituted pyrazoles and isoxazoles using a traceless "catch and release" solid-phase strategy.
An efficient three-component, two-step "catch and release" solid-phase synthesis of 3,4,5-trisubstituted pyrazoles and isoxazoles has been developed. The first step involves a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (1 or 7) with an isothiocyanate 2 and in situ immobilization of the resulting thiolate anion on Merrifield resin. Reaction of the resin-bound sulfonyl intermediate 4 with hydrazine or hydroxylamine, followed by release from the resin and intramolecular cyclization, affords 3,5-diamino-4-(arylsulfonyl)-1H-pyrazoles 5 or isoxazoles 6, respectively. Reaction of the resin-bound carbonyl intermediate 9 with hydrazine, on the other hand, leads to 3-(arylamino)-5-aryl-1H-pyrazole-4-carbonitriles 10.
Ma
Wenli
W
Department of Chemistry, Telik, Inc., 3165 Porter Drive, Palo Alto, CA 94304, USA.
Peterson
Brian
B
Kelson
Andrew
A
Laborde
Edgardo
E
D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry
D007555:Isoxazoles; D011720:Pyrazoles