合成路线:Lithiation of 6-methoxybenzothiophene (I),followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III),which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1).In a related procedure,the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2).Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2).Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1).Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX).The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).
参考文献标题:Methods for inhibiting bone loss
文献作者:Bryant,H.U.; Grese,T.A.(Eli Lilly and Company)
参考来源:EP 0651998; JP 1995188012; US 5441964
合成路线:Lithiation of 6-methoxybenzothiophene (I),followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III),which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1).In a related procedure,the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2).Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2).Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1).Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX).The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).
参考文献标题:Benzothiophenes and related cpds.as estrogen agonists
文献作者:Cameron,K.O.; Da Silva-Jardine,P.; Larson,E.R.; Hauske,J.R.; Rosati,R.L.(Pfizer Inc.)
参考来源:EP 0723537; JP 1996511273; WO 9510513
合成路线:The condensation of 1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidine (I) with 2-chloroethyl isocyanate (II) gives 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)urea (III).The nitrosation of (III) with dinitrogen tetraoxide in methylene chloride yields SLCNU.
合成路线:The nitrosation of (IV) with dinitrogen tetraoxide in methylene chloride affords (V),which is condensed with (I) to yield SLCNU.
合成路线:Lithiation of 6-methoxybenzothiophene (I),followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III),which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1).In a related procedure,the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2).Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2).Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1).Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX).The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).
参考文献标题:Methods for lowering serum cholesterol
文献作者:Bryant,H.U.; Grese,T.A.(Eli Lilly and Company)
参考来源:EP 0657162; US 5482950
合成路线:Lithiation of 6-methoxybenzothiophene (I),followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III),which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1).In a related procedure,the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2).Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2).Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1).Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX).The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).
参考文献标题:Methods for inhibiting uterine fibrosis
文献作者:Bryant,H.U.; Grese,T.A.(Eli Lilly and Company)
参考来源:EP 0650724; JP 1995188011; US 5480904
合成路线:In an alternative procedure,condensation of 4-methoxybenzaldehyde (I) with N,N-dimethyl thioformamide in the presence of LDA,followed by treatment with methanesulfonic acid leads to 6-methoxy-2-(dimethylamino)benzothiophene (II),which is subsequently acylated with 4-[2-(-1piperidino)ethoxy]benzoyl chloride (III) in hot chlorobenzene to provide the 3-benzoyl benzothiophene (IV) (6).The dimethylamino group in (IV) is displaced with cyclohexylmagnesium bromide (V) yielding (VI).Finally,methyl ether (VI) cleavage by means of AlCl3 and EtSH gives rise to the title compound (6,7).
参考文献标题:Structure-activity relationships of selective estrogen receptor modulators: Modifications to the 2-arylbenzothiophene core of raloxifene
文献作者:Grese,T.A.; Cho,S.; Finley,D.R.; Godfrey,A.G.; Jones,C.D.; Lugar,C.W.III; Martin,M.J.; Matsumoto,K.; Pennington,L.D.; Winter,M.A.; Adrian,M.D.; Cole,H.W.; Magee,D.E.; Phillips,D.L.; Rowley,E.R.; Short,L.L.; Glasebrook,A.L.; Bryant,H.U.
参考来源:J Med Chem 1997,40(2),146
合成路线:In an alternative procedure,condensation of 4-methoxybenzaldehyde (I) with N,N-dimethyl thioformamide in the presence of LDA,followed by treatment with methanesulfonic acid leads to 6-methoxy-2-(dimethylamino)benzothiophene (II),which is subsequently acylated with 4-[2-(-1piperidino)ethoxy]benzoyl chloride (III) in hot chlorobenzene to provide the 3-benzoyl benzothiophene (IV) (6).The dimethylamino group in (IV) is displaced with cyclohexylmagnesium bromide (V) yielding (VI).Finally,methyl ether (VI) cleavage by means of AlCl3 and EtSH gives rise to the title compound (6,7).
参考文献标题:Synthesis and pharmacology of 2-alkyl raloxifene analogs
文献作者:Grese,T.A.; Cho,S.; Bryant,H.U.; Cole,H.W.; Glasebrook,A.L.; Magee,D.E.; Phillips,D.L.; Rowley,E.R.; Short,L.L.
参考来源:Bioorg Med Chem Lett 1996,6(2),201
产品链接: CAS No. 150797-71-0››