新产品编号:1889417
Chemical Name: 2(R)-[4-(2,3-Dimethyl[1]benzothieno[3,2-f]benzofuran-4-yl)-2,6-diiodophenoxy]-3-phenylpropionic acid
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Oxidation of 2,3-dimethylfuran (I) under Vilsmeier conditions with POCl3 in DMF affords aldehyde (II),which is then condensed with benzothiophene (III) by means of n-BuLi in THF to provide secondary alcohol (IV).Reduction of (IV) under Nutaitis conditions with NaBH4 and TFA in THF yields methylene congener (V),which is then treated with p-anisoyl chloride (VI) under Friedel-Crafts conditions with SnCl4 in CS2 to give 1-oxa-9-thiacyclopenta[b]fluorene heterocycle (VII).Demethylation of methyl ether (VII) with BBr3 in CH2Cl2 affords phenol (VIII),which is then bis-iodinated with molecular iodine and NaOH in MeOH to yield di-iodo phenol (IX).Compound (IX) is then condensed with (S)-2-hydroxy-3-phenylpropionic acid (X) under Mitsunobu conditions with DEAD and PPh3 in benzene to furnish (R)-2-benzyl-acetic acid derivative (XI),which is finally hydrolyzed by treatment with KOH in H2O/dioxane to provide the desired product.
📌 参考资料/链接：
参考文献标题:4-Aryl-1-oxa-9-thia-cyclopenta[b]fluorenes
文献作者:Li,Z.; Wrobel,J.E.(American Home Products Corp.)
参考来源:US 6057316
📄 详细内容
合成路线:Oxidation of 2,3-dimethylfuran (I) under Vilsmeier conditions with POCl3 in DMF affords aldehyde (II),which is then condensed with benzothiophene (III) by means of n-BuLi in THF to provide secondary alcohol (IV).Reduction of (IV) under Nutaitis conditions with NaBH4 and TFA in THF yields methylene congener (V),which is then treated with p-anisoyl chloride (VI) under Friedel-Crafts conditions with SnCl4 in CS2 to give 1-oxa-9-thiacyclopenta[b]fluorene heterocycle (VII).Demethylation of methyl ether (VII) with BBr3 in CH2Cl2 affords phenol (VIII),which is then bis-iodinated with molecular iodine and NaOH in MeOH to yield di-iodo phenol (IX).Compound (IX) is then condensed with (S)-2-hydroxy-3-phenylpropionic acid (X) under Mitsunobu conditions with DEAD and PPh3 in benzene to furnish (R)-2-benzyl-acetic acid derivative (XI),which is finally hydrolyzed by treatment with KOH in H2O/dioxane to provide the desired product.
参考文献标题:Synthesis and PTP1B inhibition of novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes
文献作者:Wrobel,J.; Li,Z.; Sredy,j.; Sawicki,D.R.; Seesteller,L.; Sullivan,D.
参考来源:Bioorg Med Chem Lett 2000,10(14),1535