Synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyridinedicarboxylate
摘要:
Two syntheses of 7-trifluoromethylpyrazolo[1,5-a]pyridine dicarboxylate have been described. Approach A utilizes a nucleophilic addition of a trifluoromethyl group to N-p-toluenesulfonyliminopyridinium ylide followed by aromatization and subsequent cycloaddition with diethyl acetylenedicarboxylate to give 1b in modest yield. Approach B involves a selective zincation of pyrazolopyridine dicarboxylate at the C-7 position with (TMP)(2)Zn center dot 2LiCl.2MgCl(2) followed by iodination and trifluoromethylation to give 1b in good yield. The process in approach B has been successfully demonstrated on scale. (C) 2012 Elsevier Ltd. All rights reserved.
Palladium-Catalyzed Direct Arylations of 1,2-Azolo[1,5-<i>a</i>]pyridines using Copper(I) Chloride as a Lewis Acid Activator and the Synthesis of 2,6-Disubstituted Pyridines
作者:Kyung Hwan Oh、Seong Min Kim、Mi Jung Lee、Jin Kyoon Park
DOI:10.1002/adsc.201500726
日期:2015.12.14
A direct method for the arylation of 1,2-azolo[1,5-a]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc)2(Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5-a]pyridines and [1,2,4]triazolo[1,5-a]pyridines are arylated at ortho-positions of their pyridine
已经开发出一种直接的方法用于1,2-氮杂[1,5- a ]吡啶的芳基化。在该方法中,在作为催化剂的钯配合物Pd(OAc)2(Phen)和作为路易斯酸的氯化铜(I)(CuCl)存在下,稠合吡啶与芳基卤化物反应形成芳基化衍生物。虽然吡唑并[1,5- a ]吡啶和[1,2,4]三唑并[1,5- a ]吡啶使用这种方法在其吡啶环的邻位芳基化,但原位形成的C发生-7个芳基化的[1,5- a ]吡啶,生成2,6-二取代的吡啶。同样,用二异丙基氨基锂(LDA)处理后,C-7芳基吡唑并[1,5- a]吡啶-3-羧酸酯反应生成不同取代的2,6-二取代吡啶。最后,通过两步顺序完成顺序的C-3芳基化反应,该顺序涉及吡唑并[1,5 - a ]吡啶-3-羧酸酯的水解,然后与芳基溴化物进行双金属Pd / Cu催化的脱羧偶联反应。
Direct C7‐H Arylation of Pyrazolo[1,5‐<i>a</i>]azines with Aryl Chlorides
作者:Thanh V. Q. Nguyen
DOI:10.1002/chem.202301485
日期:2023.8.10
A new protocol for the palladium-catalyzed C−H arylation of pyrazolo[1,5-a]azines, using low-cost and abundant (hetero)arylchlorides as the coupling partners, and without any stoichiometric metal additives is reported. The structural motif of coupling products can be found in many drugs and organic materials.
报道了一种钯催化吡唑并[1,5- a ]嗪的C−H芳基化的新方案,使用低成本且丰富的(杂)芳基氯化物作为偶联伙伴,并且没有任何化学计量的金属添加剂。偶联产物的结构基序可以在许多药物和有机材料中找到。
Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein
作者:John F. Miller、Pek Y. Chong、J. Brad Shotwell、John G. Catalano、Vincent W.-F. Tai、Jing Fang、Anna L. Banka、Christopher D. Roberts、Michael Youngman、Huichang Zhang、Zhiping Xiong、Amanda Mathis、Jeffery J. Pouliot、Robert K. Hamatake、Daniel J. Price、John W. Seal、Lisa L. Stroup、Katrina L. Creech、Luz H. Carballo、Dan Todd、Andrew Spaltenstein、Sylvia Furst、Zhi Hong、Andrew J. Peat
DOI:10.1021/jm400125h
日期:2014.3.13
We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.