新产品编号:655457
Chemical Name: 2(S)-[4'-(2-Benzyl-1-benzofuran-3-yl)biphenyl-4-yloxy]-3-phenylpropionic acid
CAS No. 250341-82-3, 250341-96-9 (enantiomer)
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Condensation of 4-bromophenacyl bromide (I) with phenol in the presence of potassium carbonate produced phenoxyacetophenone (II),which was cyclized to benzofuran (III) upon treatment with polyphosphoric acid in refluxing xylene.Suzuki coupling of (III) with 4-methoxybenzeneboronic acid (IV) gave the biphenyl benzofuran (V).The phenolic derivative (VI) was prepared by demethylation of ether (V) with boron tribromide.Lithiation of (VI) with n-butyllithium,followed by addition of N-methoxy-N-methyl benzamide afforded ketone (VII),which was converted to the benzyl benzofuran (VIII) by means of a modified Wolff-Kishner reduction.Coupling of (VIII) with methyl (S)-3-phenyllactate (IX) under Mitsunobu conditions furnished the corresponding ether (X).The methyl ester group of (X) was finally hydrolyzed with NaOH to yield the title carboxylic acid.
📌 参考资料/链接：
参考文献标题:Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
文献作者:McDevitt,R.E.; Malamas,M.S.; Adebayo,F.O.(American Home Products Corp.)
参考来源:WO 9958518
📄 详细内容
合成路线:Condensation of 4-bromophenacyl bromide (I) with phenol in the presence of potassium carbonate produced phenoxyacetophenone (II),which was cyclized to benzofuran (III) upon treatment with polyphosphoric acid in refluxing xylene.Suzuki coupling of (III) with 4-methoxybenzeneboronic acid (IV) gave the biphenyl benzofuran (V).The phenolic derivative (VI) was prepared by demethylation of ether (V) with boron tribromide.Lithiation of (VI) with n-butyllithium,followed by addition of N-methoxy-N-methyl benzamide afforded ketone (VII),which was converted to the benzyl benzofuran (VIII) by means of a modified Wolff-Kishner reduction.Coupling of (VIII) with methyl (S)-3-phenyllactate (IX) under Mitsunobu conditions furnished the corresponding ether (X).The methyl ester group of (X) was finally hydrolyzed with NaOH to yield the title carboxylic acid.
参考文献标题:Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties
文献作者:Malamas,M.S.; Sredy,J.; Moxham,C.; Katz,A.; Xu,W.; McDevitt,R.; Adebayo,F.O.; Sawicki,D.R.; Seestaller,L.; Sullivan,D.; Taylor,J.R.
参考来源:J Med Chem 2000,43(7),1293
产品链接: CAS No. 250341-82-3››