Process method for preparing 2-amino-9H-pyridino[2,3-b]indole

Abstract

The invention discloses a process method for preparing 2-amino-9H-pyridino[2, 3-b]indole, and the process method comprises the following steps: S1, preparing N,N-dibenzyl-6-halogenated pyridin-2-amine; S2, preparing 6-(1H-benzo[d] [1,2,3]triazol-1-yl)-N,N-dibenzylpyridin-2-amine; S3, preparing N,N-dibenzyl-9H-pyridino[2,3-b]indol-2-amine; and S4, preparing 2-amino-9H-pyridino[2,3-b]indole. The method is low in raw material price, safe to operate, high in reaction yield and high in product purity.

Description

technical field [0001] The invention relates to the field of preparation of mutagenic reagents, in particular to a process for preparing 2-amino-9H-pyridin[2,3-b]indole. Background technique [0002] 2-Amino-9H-pyrido[2,3-b]indole (2-Amino-9H-pyrido[2,3-b]indole, CAS: 26148-68-5), referred to as A αC(A-alpha- C), is an important mutagenesis research reagent. Since it was first isolated and its structure determined in the 1970s, its mutagenic activity has been studied more and more extensively. [0003] 2-Amino-9H-pyridine[2,3-b]indole has only one synthetic route with practical value reported so far, which is "Agricultural and Biological Chemistry" (Agricultural and Biological Chemistry, 1979, 43(3), 675-677) reported the following route in 1979: [0004] [0005] What this route adopts is a 4-step synthesis method, using 6-bromo-2-pyridinecarboxylic acid as the starting material, first coupling with o-phenylenediamine, then performing triazole ring closure with nitrou...

AI Technical Summary

Problems solved by technology

[0006] There are four more serious problems in this method: first, the main material 6-bromo-2-pyridinecarboxylic acid is expensive, and the price per kilogram is more than 6000 yuan, which leads to the production of 2-amino-9H-pyridine[2,3 -b] The high price of indole does not conform to the principle of economy, which hinders the large-scale application of this product; the second, second and third steps respectively use nitrous acid and azide compounds with poor stability, and the reaction is dangerous high toxicity, poor process safety, and unfriendly to operators; the 3rd, the second step triazole ring-closing efficiency is very low, and the reaction yield of this step of preparing 1.42g of this step intermediate in the original literature report is only 19%, while When the actual production is scaled up to 100g-level production, the yield is even lower, less than 10%.

Fourth, in the fourth step, due to the presence of amino groups with relatively high reactivity, the amount of by-products generated is relatively large, resulting in thermal decomposition of triazole and ring closure to obtain 2-amino-9H-pyridine[2,3-b]indene The yield of indole is also relatively low, and the yield of original literature production 0.15g product is only 24%

[0007] These four problems seriously limit the further application of this process, and also make it very difficult to scale up the product at the hectogram and kilogram levels

[0008] In order to solve the problems of the existing process route of 2-amino-9H-pyridine[2,3-b]indole, the key raw materials are expensive, the yield is low, the process safety is poor, and it is not friendly to operators. Inexpensive starting materials and an operator-friendly method for the synthesis of 2-amino-9H-pyridine[2,3-b]indole are of great importance

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