新产品编号:343803
Chemical Name: 4-[2,2-Dimethyl-4-(4-methylphenyl)-2H-naphtho[2,3-b]thiopyran-7-yl]benzoic acid
CAS No. 204449-02-5
项目整合开发状态: Preclinical
项目研究机构: Allergan (Originator)
合成路线:Condensation of 4-bromothiophenol (I) with 3,3-dimethylacrylic acid in the presence of piperidine gave acid (II),which was converted to the corresponding acid chloride with (COCl)2 and then cyclized by treatment with SnCl4 to the thiochromanone (III).Addition of 4-tolyllithium (IV) to ketone (III) and further dehydration of the resulting tertiary alcohol (V) upon treatment with p-toluenesulfonic acid produced the benzothiochromene (VI).After lithiation by means of BuLi,quenching with DMF produced aldehyde (VII).Subsequent Horner-Emmons condensation of (VII) with phosphonate (VIII) in the presence of BuLi yielded a mixture of E and Z olefins from which the required isomer (IX) was isolated by chromatography.Cyclization of ketal (IX) by means of SnCl4 produced the naphthothiopyran (X).The ethyl ester group of (X) was finally hydrolyzed with LiOH to yield the title carboxylic acid.
📌 参考资料/链接：
参考文献标题:Benzo[1,2-g]-chrom-3-ene and benzo[1,2-g]-thiochrom-3-ene derivatives
文献作者:Johnson,A.T.; Chandraratna,R.A.; Vuligonda,V.(Allergan,Inc.)
参考来源:EP 0948478; WO 9825875
📄 详细内容
合成路线:Condensation of 4-bromothiophenol (I) with 3,3-dimethylacrylic acid in the presence of piperidine gave acid (II),which was converted to the corresponding acid chloride with (COCl)2 and then cyclized by treatment with SnCl4 to the thiochromanone (III).Addition of 4-tolyllithium (IV) to ketone (III) and further dehydration of the resulting tertiary alcohol (V) upon treatment with p-toluenesulfonic acid produced the benzothiochromene (VI).After lithiation by means of BuLi,quenching with DMF produced aldehyde (VII).Subsequent Horner-Emmons condensation of (VII) with phosphonate (VIII) in the presence of BuLi yielded a mixture of E and Z olefins from which the required isomer (IX) was isolated by chromatography.Cyclization of ketal (IX) by means of SnCl4 produced the naphthothiopyran (X).The ethyl ester group of (X) was finally hydrolyzed with LiOH to yield the title carboxylic acid.
参考文献标题:A new class of potent RAR antagonists: Dihydroanthracenyl,benzochromenyl and benzothiochromenyl retinoids
文献作者:Vuligonda,V.; Standeven,A.M.; Escobar,M.; Chandraratna,R.A.S.
参考来源:Bioorg Med Chem Lett 1999,9(5),743