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

A compound, bipyridine technology, applied in the field of drug synthesis, can solve the problems of inapplicability to large-scale industrial production, instability of cuprous salt, inconvenient storage of raw materials, etc., and achieve the effects of simplified post-processing, easy recovery, and convenient storage

Inactive Publication Date: 2014-05-21
SHANGHAI DESANO CHEM PHARMA
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method for 5,11-dihydro-6H-bispyridino-[3,2-b:2',3'-e][1,4]diazepines
  • Preparation method for 5,11-dihydro-6H-bispyridino-[3,2-b:2',3'-e][1,4]diazepines
  • Preparation method for 5,11-dihydro-6H-bispyridino-[3,2-b:2',3'-e][1,4]diazepines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]

[0029] Formula III compound 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridinecarboxamide (28.2g, 0.1mol), cyclopropylamine (15.0mL, 0.21mol), carbonic acid Sodium (11.66g, 0.11mol) and fresh copper powder (0.28g, 0.04mol) were added in 280mL of dichloromethane, under argon atmosphere, stirred and reacted at room temperature for 8 hours; the reaction was completed, filtered, and the filtrate was concentrated to obtain a brown solid 30.0 g is the compound of formula IVa, which is directly used in the next step reaction.

[0030] Add sodium hydride (11g, 0.46mol) and 100mL diethylene glycol dimethyl ether into the reaction flask, heat to 120°C, add the crude compound of the above-mentioned formula IVa, and keep the reaction for 1 hour; Methyl ether, add 200mL water at room temperature, stir until the solids are completely dissolved, then add 100mL cyclohexane, add glacial acetic acid dropwise under stirring to adjust the pH value to 7-8, precipitate solids, filter w...

Embodiment 2

[0032] Reaction formula is with embodiment 1.

[0033] Formula III compound 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridinecarboxamide (28.2g, 0.1mol), cyclopropylamine (15.0mL, 0.21mol), tris Ethylamine (16.7mL, 0.12mol) and fresh copper powder (0.28g, 0.04mol) were added to 280mL of ethyl acetate, under an argon atmosphere, stirred at room temperature for 8 hours; after the reaction was completed, filtered, and the filtrate was concentrated to obtain a brown solid 29.5g, namely the compound of formula IVa, was directly used in the next step reaction.

[0034] Add sodium hydride (11g, 0.46mol) and 100mL diethylene glycol dimethyl ether into the reaction flask, heat to 120°C, add the crude compound of the above-mentioned formula IVa, and keep the reaction for 1 hour; Methyl ether, add 200mL water at room temperature, stir until the solids are completely dissolved, then add 100mL cyclohexane, add glacial acetic acid dropwise under stirring to adjust the pH value to 7-8, pr...

Embodiment 3

[0036] Reaction formula is with embodiment 1.

[0037]Formula III compound 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridinecarboxamide (28.2g, 0.1mol), cyclopropylamine (15.0mL, 0.21mol), carbonic acid Sodium (11.66g, 0.11mol) and fresh iron powder (0.30g, 0.05mol) were added in 280mL of dichloromethane, under argon atmosphere, stirred and reacted at room temperature for 8 hours; the reaction was completed, filtered, and the filtrate was concentrated to obtain a brown solid 20.0 g is the compound of formula IVa, which is directly used in the next step reaction.

[0038] Add sodium hydride (11g, 0.46mol) and 100mL diethylene glycol dimethyl ether into the reaction flask, heat to 120°C, add the crude compound of the above-mentioned formula IVa, and keep the reaction for 1 hour; Methyl ether, add 200mL water at room temperature, stir until the solids are completely dissolved, then add 100mL cyclohexane, add glacial acetic acid dropwise under stirring to adjust the pH value to...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

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...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D471/14
CPCC07D471/14
Inventor 李金亮赵楠刘澍
Owner SHANGHAI DESANO CHEM PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap