Versatile and efficient solid-phase syntheses of pyrazoles and isoxazoles.
[reaction: see text] Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 2, followed by cyclization with hydrazines or hydroxylamine, activation of the linker, and cleavage using amines provides highly substituted, isomeric pyrazoles or isoxazoles 5. This general method gives products in excellent yields and purities in which the ratio of the two isomers can be easily controlled. A variation of this scheme generates 1,4,5- and 1,3, 4-trisubstituted pyrazoles and related isoxazoles. Post-cleavage reduction with borane converts pyrazole amides to amines such as 11.
Shen
D M
DM
Department of Molecular Design and Diversity, Merck Research Laboratories, P.O. Box 2000 RY800-C306, Rahway, New Jersey 07065, USA. dongming_shen@merck.com
Shu
M
M
Chapman
K T
KT
D007555:Isoxazoles / Q000138:chemical synthesis*; D011720:Pyrazoles / Q000138:chemical synthesis*
D007555:Isoxazoles; D011720:Pyrazoles