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Centchroman, Ormeloxifene, 6720-CDRI, Centron, Saheli, Choice 7

苯并吡喃 Chemical Name: (?-trans-1-[2-[4-(7-Methoxy-2,2-dimethyl-3-phenyl-3,4-dihydro-2H-1-benzopyran-4-yl)phenoxy]ethyl]pyrrolidine; (?-trans-7-Methoxy-2,2-dimethyl-3-phenyl-4-[4-(2-pyrrolidinoethoxy)phenyl]chromane; (?-trans-1-[2-[4-(7-Methoxy-2,2-dimethyl-3-phenyl-4-chromanyl)phenoxy]ethyl]pyrrolidine
CAS No. 78994-24-8, 31477-60-8 (trans-isomer)
项目整合开发状态: Launched-1991
项目研究机构: Central Drug Research Institute (Originator), Hindustan Latex (Licensee), ZymoGenetics (Licensee)
合成路线:The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II),which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III).This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF.The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V),which is finally isomerized with n-butyllithium in DMSO.

合成路线:The Grignard reaction of trans-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (VI) with methylmagnesium iodide (A) in THF gives a mixture of cis-2,2-dimethyl-3-phenyl-4-p-hydroxy-phenyl-7-methoxychromane (VII) and threo-2-methyl-3-phenyl-4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (VIII),which can be cyclized to (VII) with PPA at 75-80 C.Finally,(VII) is condensed with N-(2-chloroethyl)-pyrrolidine (B) by means of K2CO3 in refluxing acetone.
📌 参考资料/链接:
参考文献标题:Centchroman
文献作者:Castar,J.; Hillier,K.
参考来源:Drugs Fut 1977,2(7),441

📄 详细内容


合成路线:The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II),which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III).This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF.The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V),which is finally isomerized with n-butyllithium in DMSO.

合成路线:The Grignard reaction of trans-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (VI) with methylmagnesium iodide (A) in THF gives a mixture of cis-2,2-dimethyl-3-phenyl-4-p-hydroxy-phenyl-7-methoxychromane (VII) and threo-2-methyl-3-phenyl-4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (VIII),which can be cyclized to (VII) with PPA at 75-80 C.Finally,(VII) is condensed with N-(2-chloroethyl)-pyrrolidine (B) by means of K2CO3 in refluxing acetone.

参考文献标题:Antifertility agents.12.Structure-activity relationship of 3,4-diphenylchromenes and -chromans
文献作者:Ray,S.; Grover,P.K.; Kamboj,V.P.; Setty,B.S.; Kar,A.B.; Anand,N.
参考来源:J Med Chem 1976,19(2),276-279


合成路线:The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II),which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III).This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF.The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V),which is finally isomerized with n-butyllithium in DMSO.

参考文献标题:Proc閐?de pr閜aration de 3,4-(diph閚yl)-chromanes substitu閟
文献作者:Bolger,J.W.
参考来源:DE 2329201; FR 2187777


合成路线:The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II),which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III).This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF.The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V),which is finally isomerized with n-butyllithium in DMSO.
参考文献标题:Process for preparation of substituted 3,4-(diphenyl)chromans
文献作者:Bolger,J.W.
参考来源:US 3822287


产品链接: CAS No. 78994-24-8››

产品链接: CAS No.31477-60-8››