Azaindole with regionselectivity and synthetic method thereof

A regioselective, azaindole technology, applied in the field of azaindole and its synthesis, can solve the problems of low reaction yield of diethylene glycol and the like

Inactive Publication Date: 2014-03-12
上海药明康德新药开发有限公司 +2
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When we synthesized according to this method, we found that the

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
  • Azaindole with regionselectivity and synthetic method thereof
  • Azaindole with regionselectivity and synthetic method thereof
  • Azaindole with regionselectivity and synthetic method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1 : 2-Bromo-6,7,8,9-tetrahydro-5H-pyrido[3,2,b]indole preparation of

[0069]

[0070] Steps:

[0071] React 2-bromo-5-fluoropyridine (4 g, 23 mmol) and 10 ml of hydrazine hydrate with a microwave oven at 110 ° C for 1 hour. After cooling, pour the reaction solution into 60 ml of water to precipitate a solid, filter, and dry the filter cake to obtain 2 grams of 2-bromo-5-hydrazine pyridine, yield 47%.

[0072] 1 H NMR (400MHz, CDCl 3 ) d : 7.99 (br. s., 1H), 7.30 (s, 1H), 7.11 (d, J =8.0 Hz, 1H), 5.28 (s, 1H), 3.64 (s, 2H).

[0073] 2-bromo-5-hydrazine pyridine (2 g, 11 mmol) and cyclohexyl ketone (1.15 g, 12 mmol) were reacted in 15 ml of ethanol to water four to one at room temperature for 1 hour, and the solid was filtered to obtain 0.77 Gram 2-bromo-5-cyclohexylhydrazonepyridine, yield 28%.

[0074] 1 H NMR (400MHz, CDCl 3 ) d : 8.07 (s, 1H), 7.39 - 7.33 (m, 1H), 7.33 - 7.29 (m, 1H), 7.07 (s, 1H), 2.37 - 2.31 (m, 4H), 1.91 - 1.99 (m, 2H) , 1...

Embodiment 2

[0077] Example 2 : 5-Bromo-2,3-dimethyl-1H-pyrrolo[3,2,b]pyridine preparation of

[0078]

[0079] Steps:

[0080] 2-bromo-5-hydrazinopyridine (8 g, 46.2 mmol) and butan-2-ketone (5 g, 69.4 mmol) were reacted in 65 ml of ethanol at room temperature for 18 hours, and the reaction solution was concentrated under pressure to obtain 4.34 g of 2 - Crude bromo-5-(2-(butan-2-hydrazone)pyridine.

[0081] Put 4.34 grams of crude product 2-bromo-5-(2-(butyl-2-hydrazone)pyridine in 15 ml of heat-conducting oil, react with microwave at 250°C for 10 minutes, and put the reaction liquid directly on the silica gel column after cooling. About 20 to 1 ester was used as the eluent, and the collected fractions were concentrated under reduced pressure to obtain 2.8 g of 5-bromo-2,3-dimethyl-1H-pyrrolo[3,2,b]pyridine, with a yield of 69%.

[0082] 1 H NMR (400MHz, CDCl 3 ) δ : 7.37 (d, J =8.1 Hz, 1H), 7.14 (d, J =8.1 Hz, 1H), 2.42(s, 3H), 2.37(s, 3H).

Embodiment 3

[0083] Example 3 : 5-bromo-3-isopropyl-1H-pyrrolo[3,2,b]pyridine preparation of

[0084]

[0085] Steps:

[0086] 2-Bromo-5-hydrazine pyridine (5 g, 26.6 mmol) and 3-methylbutyraldehyde (3.44 g, 39.9 mmol) were reacted at room temperature in 50 ml of ethanol for 18 hours, and the reaction solution was concentrated under pressure to obtain 3.8 g of crude 2-bromo-5-(2-(3-methylbutylhydrazone)pyridine.

[0087] Put 3.8 grams of crude product 2-bromo-5-(2-(3-methylbutylhydrazone)pyridine in 15 ml of heat-conducting oil, react with microwave at 250°C for 10 minutes, and put the reaction liquid directly on the silica gel column after cooling, petroleum ether ratio About 20:1 ethyl acetate was used as the eluent, and the collected fractions were concentrated under reduced pressure to obtain 1.7 g of 5-bromo-3-isopropyl-1H-pyrrolo[3,2,b]pyridine, with a yield of 49%.

[0088] 1 H NMR (400MHz, CDCl 3 ) δ : 7.48 (d, J =8.1 Hz, 1H), 7.22 (s, 1H), 7.19 (d, J =8.1 Hz, 1H), 3...

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 relates to azaindole with regioselectivity and a synthetic method thereof, and mainly solves the technical problems that no document reports the synthesis of azaindole with regioselectivity, and the structure-function relationship of the pharmaceutical activity of the azaindole is screened. The structure general formula is as follows (as shown in the specification), R1 and R2 are substituent groups on the pentabasic pyrrole ring of the azaindole, and can be hydrogen, straight chains, side chains or ring-shaped alkyl groups, R3 is an alkyl group on the hexahydric n-heterocyclic of the azaindole, a halogen substituent group or a hydrogen atom without substitution, and A is one of carbon atom or nitrogen heteroatom.

Description

technical field [0001] The invention relates to an azaindole and a synthesis method thereof, in particular to an azaindole with high regioselectivity and a synthesis method thereof. Background technique [0002] Indole compounds are an important class of pharmaceutical intermediates. Indole is a building block of the natural amino acid tryptophan and the important neurotransmitter serotonin. Many natural products and synthetic pharmaceutical small molecules contain indole groups. [0003] As the bioisostere of indole, azaindole has attracted more and more attention. [0004] The review on the synthesis of azaindole mainly includes "Synthesis and Reaction of 4,5,6-Azaindole" published in Tetrahedron (Tetrahedron) pp. 8689-8707 in 2007 by Beno?t Joseph, and Mérour Jean-Yves, "Synthesis and Reaction of 7-Azaindole", 2001, Current Organic Chemistry, pp. 471-506. Organometallic-mediated azaindole synthesis is an important class of azaindole synthesis methods, as reviewed by J...

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): C07D471/04C07D487/04A61P1/00
CPCC07D471/04C07D487/04
Inventor 石卫华江志赶邹文慧韩丽霞韩太平贺海鹰陈曙辉
Owner 上海药明康德新药开发有限公司
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