Use of a Curtius Rearrangement as Part of the Multikilogram Manufacture of a Pyrazine Building Block,Organic Process Research & Development

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Use of a Curtius Rearrangement as Part of the Multikilogram Manufacture of a Pyrazine Building Block
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2017-12-12 00:00:00 , DOI: 10.1021/acs.oprd.7b00340
Alan Steven ₁ , Phillip Hopes ₂

Affiliation

Commercial route definition for a glucokinase activator called for a reevaluation of the synthesis and processes used to access multikilogram quantities of 2-amino-5-methylpyrazine. After consideration of different options, a variation of the Curtius rearrangement used by the medicinal chemistry route was selected for further development. The formation of an acyl azide for the Curtius rearrangement required a process safety control strategy to be put in place. The process developed was used to successfully deliver multikilogram quantities of 2-amino-5-methylpyrazine in an overall yield of 68%, starting from 5-methylpyrazine-2-carboxylic acid.

中文翻译：

使用Curtius重排作为吡嗪构建基团的多千克生产的一部分

葡萄糖激酶激活剂的商业路线定义要求重新评估用于获取多千克量的2-氨基-5-甲基吡嗪的合成和工艺。在考虑了不同的选择之后，选择了用于药物化学路线的库尔修斯重排的变化形式，以进行进一步的开发。库尔修斯重排的酰基叠氮化物的形成需要采取过程安全控制策略。从5-甲基吡嗪-2-羧酸开始，开发的工艺用于成功交付总重量达68％的多千克量的2-氨基-5-甲基吡嗪。

更新日期：2017-12-12

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