Chemical Name: 3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine hydrochloride
项目整合开发状态: Launched
项目研究机构: Merck & Co. (Originator), Vela Pharmaceuticals (Not Determined), Alza (Licensee)
合成路线:The starting product dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) is prepared by condensation of phthalic anhydride (X) with phenylacetic acid (XI) by means of sodium acetate at 240 C that gives benzalphthalide (XII).This compound is reduced with red phosphorus in refluxing aqueous HI yielding 2-(2-phenylethyl)benzoic acid (XIII),which is then cyclized with polyphosphoric acid at 175 C afforing dibenzo[a,d]cyclohepta-1,4-diene-5-one (XIV).The ketone (XIV) is brominated with NBS in CCl4 to the bromo ketone (XV) and finally dehydrobrominated with triethylamine.
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with dimethylaminopropyl magnesium (C) chloride in ethyl ether gives 5-hydroxy-5-(3-dimethylaminopropyl)dibenzo[a,d]cyclohepta-1,4,6-triene (IV),which is then treated with HCl in refluxing acetic acid.Alternatively,it can also be obtained by methylation of 5-(3-methylaminopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (IX) with formic acid and formaldehyde at 100 C.
📄 详细内容
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with allyl magnesium bromide (A) in ethyl ether gives 5-hydroxy-5-allyldibenzo[a,d]cyclohepta-1,4,6-triene (II),which is dehydrated with acetic anhydride and acetyl chloride at 90 C yielding 5-propenylidenedibenzo[a,d]cyclohepta-1,4,6-triene (III).Finally,this compound is treated with phenylmagnesium bromide and dimethylamine (B) at 80 C.
参考文献标题:A process for the manufacture of tricyclic amines
文献作者:Schmitt,G.(F.Hoffmann-La Roche AG)
参考来源:BE 0636000; CH 385191; DE 1468006; FR 1366413; GB 990105
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with dimethylaminopropyl magnesium (C) chloride in ethyl ether gives 5-hydroxy-5-(3-dimethylaminopropyl)dibenzo[a,d]cyclohepta-1,4,6-triene (IV),which is then treated with HCl in refluxing acetic acid.Alternatively,it can also be obtained by methylation of 5-(3-methylaminopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (IX) with formic acid and formaldehyde at 100 C.
参考文献标题:
文献作者:Protiva,M.; Vera,S.
参考来源:CZ 136585
合成路线:The starting product dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) is prepared by condensation of phthalic anhydride (X) with phenylacetic acid (XI) by means of sodium acetate at 240 C that gives benzalphthalide (XII).This compound is reduced with red phosphorus in refluxing aqueous HI yielding 2-(2-phenylethyl)benzoic acid (XIII),which is then cyclized with polyphosphoric acid at 175 C afforing dibenzo[a,d]cyclohepta-1,4-diene-5-one (XIV).The ketone (XIV) is brominated with NBS in CCl4 to the bromo ketone (XV) and finally dehydrobrominated with triethylamine.
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with allyl magnesium bromide (A) in ethyl ether gives 5-hydroxy-5-allyldibenzo[a,d]cyclohepta-1,4,6-triene (II),which is dehydrated with acetic anhydride and acetyl chloride at 90 C yielding 5-propenylidenedibenzo[a,d]cyclohepta-1,4,6-triene (III).Finally,this compound is treated with phenylmagnesium bromide and dimethylamine (B) at 80 C.
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with dimethylaminopropyl magnesium (C) chloride in ethyl ether gives 5-hydroxy-5-(3-dimethylaminopropyl)dibenzo[a,d]cyclohepta-1,4,6-triene (IV),which is then treated with HCl in refluxing acetic acid.Alternatively,it can also be obtained by methylation of 5-(3-methylaminopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (IX) with formic acid and formaldehyde at 100 C.
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with cyclopropyl magnesium bromide (D) in THF gives 5-hydroxy-5-cyclopropyldibenzo[a,d]cyclohepta-1,4,6-triene (V),which is then treated with HBr in acetic acid to yield 5-(3-bromopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VI).Finally,(VI) is treated with dimethylamine (B) in benzene at 95 C.The hydroxycompound (V),obtained as before,is treated with HClO4 in dioxane to yield 5-(3-hydroxypropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VII),which is then treated with p-toluenesulfonyl chloride in pyridine to afford the tosyl derivate (VIII).Finally,(VIII) is treated with dimethylamine (B) in benzene at 100 C.
参考文献标题:Cyclobenzaprine
文献作者:Roberts,P.J.; Casta馿r,J.
参考来源:Drugs Fut 1977,2(5),299
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with cyclopropyl magnesium bromide (D) in THF gives 5-hydroxy-5-cyclopropyldibenzo[a,d]cyclohepta-1,4,6-triene (V),which is then treated with HBr in acetic acid to yield 5-(3-bromopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VI).Finally,(VI) is treated with dimethylamine (B) in benzene at 95 C.The hydroxycompound (V),obtained as before,is treated with HClO4 in dioxane to yield 5-(3-hydroxypropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VII),which is then treated with p-toluenesulfonyl chloride in pyridine to afford the tosyl derivate (VIII).Finally,(VIII) is treated with dimethylamine (B) in benzene at 100 C.
参考文献标题:Nouveaux d閞iv閟 de dibenzocyclohept鑞es et leur pr閜aration
文献作者:Hoffsommer,R.D.Jr.; et al.
参考来源:BE 0631012
合成路线:The Grignard reaction of dibenzo[a,d]cyclohepta-1,4,6-triene-5-one (I) with cyclopropyl magnesium bromide (D) in THF gives 5-hydroxy-5-cyclopropyldibenzo[a,d]cyclohepta-1,4,6-triene (V),which is then treated with HBr in acetic acid to yield 5-(3-bromopropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VI).Finally,(VI) is treated with dimethylamine (B) in benzene at 95 C.The hydroxycompound (V),obtained as before,is treated with HClO4 in dioxane to yield 5-(3-hydroxypropylidene)dibenzo[a,d]cyclohepta-1,4,6-triene (VII),which is then treated with p-toluenesulfonyl chloride in pyridine to afford the tosyl derivate (VIII).Finally,(VIII) is treated with dimethylamine (B) in benzene at 100 C.
参考文献标题:Dibenzocyclohept鑞es
文献作者:Wendler,N.L.
参考来源:BE 0633316