Preparation method for 5,11-dihydro-6H-bispyridino-[3,2-b:2',3'-e][1,4]diazepines

Abstract

The invention discloses a preparation method for 5,11-dihydro-6H-bispyridino-[3,2-b:2',3'-e][1,4]diazepines. The method comprises a step of subjecting a compound represented by a formula III and monosubstituted amine to a coupling reaction under the catalysis of a metal catalyst so as to produce a compound represented by a general formula IV and a step of subjecting the compound represented by the general formula IV to an intramolecular cyclization reaction to produce a compound represented by a general formula I. Concrete reaction route is described in the specification. According to the invention, copper / iron metal catalysis is creatively employed for preparation of a target object, construction of a carbon-nitrogen bond by using copper / iron metal catalysis under mild conditions is realized, and technical biases are overcome; as a copper / iron metal is used as a catalyst, the advantages of convenient storage, a cheap price, wide sources, easy recovery and the like are obtained, the usage amount of monosubstituted amine is reduced, post-treatment is simplified, cost is saved, and the method is more applicable to industrial large-scale production and has a better industrial practical value.

Description

technical field [0001] The invention relates to a method for preparing 5,11-dihydro-6H-bipyrido[3,2-b:2',3'-e][1,4]diazepine compounds, which belongs to the pharmaceutical synthesis technology field. Background technique [0002] AIDS, Acquired Immune Deficiency Syndrome, English name Acquired Immune Deficiency Syndrome, (AIDS), is human immunodeficiency caused by human immunodeficiency virus (Human Immunodeficiency Virus, HIV), and a series of opportunistic infections and tumors, A syndrome that can lead to death in severe cases. HIV was first discovered in humans in 1983. At present, AIDS has changed from a fatal disease to a controllable chronic disease, and has become a public health problem that seriously threatens the health of people all over the world. [0003] 5,11-Dihydro-6H-bispyrido[3,2-b:2',3'-e][1,4]diazepines are a class of HIV-1 compounds developed by Boehringer Ingelheim Non-nucleoside reverse transcriptase inhibitors, the general chemical structure of w...

AI Technical Summary

Problems solved by technology

In these methods, in order to avoid the volatilization of cyclopropylamine, it needs to be carried out in an autoclave during the condensation process with the compound of formula II, and the reaction temperature is all at 140 ° C, which not only makes the energy consumption of the production process high, but also has certain dangers. Not suitable for industrialized mass production

[0009] Later studies found that cuprous salts could be used to build carbon-nitrogen bonds. For example, the reaction of the compound of formula III disclosed in Chinese patent ZL200810107893.4 with cyclopropylamine uses cuprous halide as a catalyst, although the method catalyzed by cuprous salts can make the reaction The conditions are mild, but because the cuprous salt is unstable, this will cause inconvenience to the storage of raw materials, and will adversely affect the progress of the reaction, and it is not suitable for large-scale industrial production.

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