Ma Wenli, Peterson Brian, Kelson Andrew, Laborde Edgardo
Department of Chemistry, Telik, Inc., 3165 Porter Drive, Palo Alto, CA 94304, USA.
J Comb Chem. 2009 Jul-Aug;11(4):697-703. doi: 10.1021/cc900045t.
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.
已开发出一种高效的三组分两步“捕获与释放”固相合成3,4,5-三取代吡唑和异恶唑的方法。第一步涉及2-磺酰基或2-羰基乙腈衍生物（1或7）与异硫氰酸酯2在碱促进下的缩合反应，以及所得硫醇盐阴离子在Merrifield树脂上的原位固定。树脂结合的磺酰基中间体4与肼或羟胺反应，随后从树脂上释放并进行分子内环化，分别得到3,5-二氨基-4-（芳基磺酰基）-1H-吡唑5或异恶唑6。另一方面，树脂结合的羰基中间体9与肼反应，生成3-（芳基氨基）-5-芳基-1H-吡唑-4-甲腈10。
