US EPA

7441081 

Journal Article 

Synthesis and analgesic activity of some substituted 1-benzofurans and 1-benzothiophenes 

Radl, S; Hezky, P; Konvicka, P; Krejci, I 

2000 

1 

Collection of Czechoslovak Chemical Communications
ISSN: 0010-0765
EISSN: 1212-6950 

Czech Academy of Sciences 

65 

7 

1093-1108 

English 

10.1135/cccc20001093 

WOS:000089439500004 

http://cccc.uochb.cas.cz/65/7/1093/
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2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzofuran-3-amines were prepared from 2-hydroxybenzonitrile and corresponding bromoethanone derivatives. 2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-1-benzofuran-3-amine treated with acetic anhydride or ethyl chloroformate provided the corresponding N -acetyl or N -ethoxycarbonyl derivatives. These N -activated compounds were alkylated with ethyl bromoacetate to provide ethyl N -acetyl- N -(2-benzoyl-1-benzofuran-3-yl)glycinate and ethyl N -(2-benzoyl-1-benzofuran-3-yl)- N -ethoxycarbonylglycinate, respectively. Their mild hydrolysis gave the corresponding glycine derivatives. Methylation of ethyl N -(2-benzoyl-1-benzofuran-3-yl)carbamate gave the corresponding N -methyl carbamate, which was hydrolyzed to N -methyl-(2-benzoyl-1-benzofuran-3-yl)amine. 2-Benzoyl-7-methoxy-1-benzofuran-3-amine and 2-(4-methoxybenzoyl)-1-benzofuran-3-amine were demethylated with boron tribromide to the corresponding hydroxy derivatives; their O -alkylation with ethyl bromoacetate than gave ethyl [(3-amino-2-benzoyl-1-benzofuran-7-yl)oxy]acetate and ethyl {4-[(3-amino-1-benzofuran-2-yl)carbonyl]phenoxy}acetate, respectively. The mild hydrolysis of these esters provided corresponding acids. Similarly, alkylation of the hydroxy derivatives with (dimethylamino)propyl chloride gave corresponding (dimethylamino)propoxy derivatives. 2-Hydroxybenzonitrile treated with 2-bromo-1-(2-, 3-, or 4-pyridyl)ethan-1-one provided the respective 2-(pyridylcarbonyl)-1-benzofuran-3-amine. Similar 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-3-(bromomethyl)-1-benzofuran treated with dimethylamine, 1-methylpiperazine, and sodium 1-methylpiperidine-4-thiolate gave the corresponding alkylation products. Several compounds were found to exhibit considerable analgesic activity. 

benzofurans; benzothiophenes; heterocyclizations; demethylations; alkylations; antinociceptive activity; analgesics