Method for catalyzing amino protection by imidazole hydrochloride

Abstract

The invention provides an amino protection method which realizes multi-substituted amino protection by using imidazole hydrochloric acid as an accelerator to push derivatives of primary amine, secondary amine and acrylamide to perform Michael addition at a relatively low temperature, wherein the imidazole hydrochloric acid promotes a carbon-nitrogen bond to crack back to the derivatives of primaryamine and acrylamide at a high temperature. The method provided by the invention is simple and economical, high in practicability, free of any other catalysts or additives, capable of protecting amino to have good functional group tolerance and excellent yield and purity, short in reaction time, free from harsh reaction conditions and suitable for industrial production.

Description

technical field [0001] The present invention relates to the protection of amino groups, in particular to a method of using imidazole hydrochloride to promote the Michael addition of derivatives of primary amines, secondary amines and acrylamide, the addition occurs at a lower temperature, and the carbon-nitrogen bond breaks at a high temperature Going back to the raw materials, methods of forming primary and secondary amines. Background technique [0002] Many drug intermediates or active molecules usually contain amino groups, but the stability of amino groups is poor and the groups are easily oxidized, so amino groups often need to be protected during drug synthesis. Traditionally, amines were reacted with benzyl chloroformate in the presence of inorganic bases (Yang, B.; Shi, L.; Wu, J. et al. Tetrahedron 2013, 69, 3331; Spaulding, A.; Takrouri, K. ; Mahalingam,P., et al.Bioorg Med Chem Lett. 2017,27,5310.), di-tert-butyl dicarbonate (Samadi,S.; Jadidi,K.; Khanmohammadi,...

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Problems solved by technology

However, most of these reactions suffer from problems such as high cost, corrosion and toxicity

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