4-substituted amino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and preparing method

A technology of methoxycarbonylbenzene and 3-d, which is applied in the field of medicine and chemical industry, can solve the problems of unreported synthesis methods, high toxicity of reaction reagents, harsh reaction conditions, etc., and achieve large-scale preparation, easy large-scale preparation, The effect of mild reaction conditions

Inactive Publication Date: 2016-04-06
SUN YAT SEN UNIV +1
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the reported synthesis methods of benzofuropyrimidines mainly include the following: (1) Electrochemical oxidation of 3,4-dihydroxybenzoic acid and coupling of 1,3-dimethylbarbituric acid Decarboxylation reaction (J.Org.Chem., 2002, 67, 5036-5039), but this type of method requires special electrode materials, long reaction time, and narrow substrate applicability; (2) o-methoxyarylboronic acid compounds Suzuki coupling reaction with aminopyrimidines (WO2007 / 090852A1, [P] 2007-08-16), but this method requires expensive Pd metal complexes to catalyze, the reaction conditions are harsh, and the production cost is high; (3) base Catalyzes the coupling ring closure series reaction of o-cyanophenol and α-bromocarbonyl compound (Bioorg.Med.Chem.Lett., 2013,23,2775-2780), but the reaction reagents of this method are highly toxic and cause serious environmental pollution , and the synthetic route is longer
At present, compared with benzofuro[3,2-d]pyrimidines, there is no literature report on the synthesis method of benzofuro[2,3-d]pyrimidines, and there is no use of renewable resources for Starting materials, related reports on the preparation of 4-substituted amino-6-methoxycarbonylbenzofuro[2,3-d]pyrimidines by metal-free catalysis

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
  • 4-substituted amino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and preparing method
  • 4-substituted amino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and preparing method
  • 4-substituted amino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and preparing method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: Preparation of 4-(p-toluidyl)-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine

[0030] Add methyl 2-amino-3-cyanobenzofuran-5-carboxylate (0.22g, 1.0mmol), triethyl orthoformate (0.17ml, 1.0mmol), 8ml of toluene and a catalytic amount of glacial acetic acid into the flask , reflux at 60°C for 1 hour, concentrate and remove the solvent after the reaction is complete, add p-toluidine (0.16 g, 1.5 mmol) and 8 ml of glacial acetic acid to the solid obtained above, reflux at 120°C for 6 hours, and add 40 ml of In water, fully stirred and then filtered, the resulting solid was recrystallized from ethyl acetate and petroleum ether to obtain 0.193 g of a white solid, with a yield of 58.0%.

[0031] 1 HNMR (400MHz, DMSO‐d 6 )δ: 9.70(s,1H), 8.82(s,1H), 8.51(s,1H), 8.12(dd,J 1 =8.40Hz,J 2 =1.60Hz,1H),7.85(d,J=8.40Hz,1H),7.47(d,J=8.00Hz,2H),7.23(d,J=8.40Hz,2H),3.91(s,3H), 2.34(s,3H); 13 CNMR (100MHz, DMSO‐d 6 )δ: 169.1, 166.1, 156.3, 156.2, 154.2, 135.9, 134.0, 129.0,...

Embodiment 2

[0032] Example 2: Preparation of 4-(p-toluidyl)-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine

[0033]Add methyl 2-amino-3-cyanobenzofuran-5-carboxylate (0.22g, 1.0mmol), triethyl orthoformate (0.50ml, 3.0mmol), 8ml of toluene and a catalytic amount of glacial acetic acid into the flask , reflux at 60°C for 1 hour, concentrate and remove the solvent after the reaction is complete, add p-toluidine (0.16 g, 1.5 mmol) and 8 ml of glacial acetic acid to the solid obtained above, reflux at 120°C for 6 hours, and add 40 ml of In water, fully stirred and then filtered, the obtained solid was recrystallized with ethyl acetate and petroleum ether to obtain 0.216 g of white solid, with a yield of 65.0%.

[0034] The structural analysis data are the same as in Example 1.

Embodiment 3

[0035] Example 3: Preparation of 4-(p-toluidyl)-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine

[0036] Add methyl 2-amino-3-cyanobenzofuran-5-carboxylate (0.22g, 1.0mmol), triethyl orthoformate (0.50ml, 3.0mmol), 8ml of toluene and a catalytic amount of glacial acetic acid into the flask , reflux at 110°C for 1 hour, concentrate and remove the solvent after the reaction is complete, add p-toluidine (0.16g, 1.5mmol) and 8ml of glacial acetic acid to the solid obtained above, reflux at 120°C for 6h, and add 40ml of In water, fully stirred and then filtered, the obtained solid was recrystallized with ethyl acetate and petroleum ether to obtain 0.247 g of white solid, with a yield of 74.1%.

[0037] The structural analysis data are the same as in Example 1.

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 4-substituted mino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and a preparing method thereof. 2-amino-3-cyano benzofuran-5-carboxylic acid methyl ester and ortho-formate are dissolved into a solvent A, a reaction is conducted under the acid catalysis and heating conditions, and concentration is carried out after the reaction is finished to obtain an intermediate; then, the intermediate and an amine compound are subjected to a reflux reaction in a solvent B, a reaction product is subjected to separation and purification treatment, and a product is obtained. The compound has potential biological activity, important research value and good application prospects. The preparing method is mild in reaction condition, easy to implement, short in reaction time, high in yield and low in cost, and mass preparation can be easily achieved.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a 4-substituted amino-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine compound and a preparation method thereof. Background technique [0002] Benzofuropyrimidine derivatives are a class of fused heterocyclic compounds with good biological activity, for example: N-(3-bromophenyl)-benzofuro[3,2-d]pyrimidine (structural formula A) has Inhibitory activity of epidermal growth factor receptor tyrosine kinase (J.Med.Chem.1999, 42, 5464-5474); 4-Alkylamino-8-methylsulfonylbenzofuro[3,2-d]pyrimidine -2-amine (structural formula B) is a histamine H 4 Receptor modulator with antihistamine H 4 Mediated various immune and inflammatory reactions and other activities (EP2020412A1, [P] 2009-02-04); derivatives of benzofuro[3,2-d]pyrimidin-2-one (structural formula C) can inhibit HIV The expression of -1 reverse transcriptase has better anti-HIV-1 virus activity (Bioorg. Med. Chem. L...

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): C07D491/048
CPCC07D491/048
Inventor 邹永盛剑飞王德建位文涛张湘东潘文杰
Owner SUN YAT SEN UNIV
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