Synthesizing method of carbolin compound

Abstract

The invention discloses a synthesizing method of a carbolin compound. The synthesizing method comprises the following steps of enabling pyridine derivatives, o-nitroaniline and o-nitroaniline derivative thereof to generate coupling and reduction reaction, or directly generate coupling reaction with benzotriazole; converting into a diazotized triazole intermediate; finally, treating the obtained intermediate after reaction under the action of a reagent, so as to obtain substituted carbolin. The synthesizing method has the characteristics that on the basis of the improved Graebe-Ullmann method,the reaction raw materials, reaction reagents and conditions are preferably selected; the selectivity of target products is enhanced, the reaction time is shortened, the reaction temperature is reduced, the number of impurities is fewer, the yield rate is high, and the like; the method is suitable for synthesizing the substituted alpha-carbolin and beta-carbolin, so as to provide a simple and reliable selection plan for the obtaining and utilization of the compound.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of carboline compounds. Background technique [0002] Carboline, also known as carboline and diazafluorene, is a heterocyclic compound in which the pyridine ring and the pyrrole ring of indole are fused. There are currently 4 isomers, of which 2-carboline is also called α-carboline and α-carbolin, and 3-carboline is also called β-carbolin. Its natural products have anti-inflammatory, bactericidal, cytotoxic, A series of biological activities such as anticancer properties, activity of central nervous system and cardiovascular system. [0003] The synthetic route of α-carbolin has been reported in several cases. In 1924, Robinson et al first reported the improved Graebe-Ullmann method to synthesize α-carbolin, that is, o-phenylenediamine and 2-chloropyridine were heated to 140°C in ethanol and then coupled with nitrous acid in an acidic environment provi...

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Problems solved by technology

[0008] Therefore, although there are many schemes for the synthesis of α-carbolin, there are still some defects, such as low yield, expensive reagents, difficulty in preparing or obtaining starting materials, or lack of flexibility, harsh reaction conditions, etc.

However, there are few synthetic methods for β-carbolin, mainly using 1-pyridylbenzotriazole intermediates to generate target compounds under the action of ultraviolet light or zinc chloride, which is difficult to operate and highly toxic, and is inconvenient for large-scale synthesis

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