6-氯咪唑并[1,2-b]哒嗪-3-甲腈的合成研究

doi:10.3976/j.issn.1002-4026.2021.01.013

Shandong Science ›› 2021, Vol. 34 ›› Issue (1): 105-112.doi: 10.3976/j.issn.1002-4026.2021.01.013

• Other Research Article • Previous Articles Next Articles

Synthesis of 6-chloroimidazo[1,2-b]pyrazine-3-carbonitrile

CHENG Wei¹，CHEN Qi-xu¹，ZHANG Xiang-long²，QI Qi¹，WANG Ming-jun¹， LIU Sheng-wei¹，YUAN Wen-peng^1*

1. Biological Engineering Technology Innovation Center of Shandong Province，Heze Branch，Qilu University of Technology (Shandong Academy of Sciences)， Heze 274000， China；2. Shandong Engineering Laboratory of Small Molecule Heterocyclic Compounds，Shandong Youbang Biochemical Technology Co., Ltd.,Heze 274000,China

Received:2020-10-09 Online:2021-02-15 Published:2021-01-31

Abstract

Abstract: 6-chloroimidazo[1,2-b]pyrazine-3-carbonitrile is a major intermediate of BMS-986260, which is a novel TGF-β R1 inhibitor that can be used as an anticancer drug. The synthesis goes through the following five-step reaction process with a total yield of 69.4%: hydrazine hydrate and maleic anhydride are considered as raw materials, acid-catalyzed condensation reaction, chlorination with phosphorus oxychloride, ammonolysis with ammonia water, imidization with N,N-dimethylformamide dimethyl acetal, and ring-closing condensation with bromoacetonitrile. The purity of the obtained product was 98.3%, which was measured via high-performance liquid chromatography (HPLC) at wavelength of 254 nm. The structure was confirmed through ¹H NMR and ¹³C NMR. Compared with the reported synthetic routes, this route exhibits good chemical selectivity, low cost, easy operation, and high yield. Further, it requires no column chromatography separation and is suitable for industrial production.

Key words: hydrazine hydrate, maleic anhydride; 6-chloroimidazo[1,2-b]pyrazine-3-carbonitrile, synthesis route

CLC Number:

R914.5

CHENG Wei, CHEN Qi-xu, ZHANG Xiang-long, QI Qi, WANG Ming-jun, LIU Sheng-wei, YUAN Wen-peng. Synthesis of 6-chloroimidazo[1,2-b]pyrazine-3-carbonitrile[J].Shandong Science, 2021, 34(1): 105-112.

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Synthesis of 6-chloroimidazo[1,2-b]pyrazine-3-carbonitrile

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