Route Selection and Optimization in the Synthesis of Two Imidazopyridine Inhibitors of DGAT-2,Organic Process Research & Development

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Route Selection and Optimization in the Synthesis of Two Imidazopyridine Inhibitors of DGAT-2
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-02-14 00:00:00 , DOI: 10.1021/acs.oprd.8b00005
Scott J. Bader ₁ , Michael Herr ₁ , Gary E. Aspnes ₁ , Shawn Cabral ₁ , Qifang Li ₁ , Jianwei Bian ₁ , Steven B. Coffey ₁ , Matthew S. Dowling ₁ , Dilinie P. Fernando ₁ , Wenhua Jiao ₁ , Sophie Y. Lavergne ₁ , Daniel W. Kung ₁

Affiliation

The scalable syntheses of two imidazopyridine inhibitors of the enzyme diacylglycerol acyltransferase 2 (DGAT-2) are described. 6-Chloro-3-nitro-2-aminopyridine was the starting material for the convergent synthesis of the central imidazopyridine ring. Differentiation in reactivity of the C2- and C3-nitrogen substituents on the pyridine ring and the development of mild cyclodehydration conditions to form the imidazole ring were critical problems that were addressed to deliver a 3-kg batch of compound 1 (PF-06424439) and a 0.1-kg batch of compound 2 (PF-06450561).

中文翻译：

两种DGAT-2咪唑并吡啶抑制剂的合成路线选择和优化

描述了酶二酰基甘油酰基转移酶2（DGAT-2）的两种咪唑并吡啶抑制剂的可扩展合成方法。6-氯-3-硝基-2-氨基吡啶是收敛合成中央咪唑并吡啶环的起始原料。吡啶环上C2-和C3-氮取代基的反应性差异以及形成咪唑环的温和环脱水条件的发展是关键问题，已解决了要交付3千克批次的化合物1（PF-06424439）和一批0.1千克的化合物2（PF-06450561）。

更新日期：2018-02-14

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