Chemical Name: 2-[3-(4-Fluorobenzoyl)-1-propyl]-5alpha,9alpha-dimethyl-2'-hydroxy-6,7-benzomorphan; 3-[3-(4-Fluorobenzoyl)-1-propyl]-1,2,3,4,5,6-hexahydro-8-hydroxy-6,11-dimethyl-2,6-methano-3-benzazocine; (2alpha,6alpha,11R*)-1-(4-Fluorophenyl)-4-(1,4,5,6-tetrahydro-8-hydroxy-6,11-dimethyl-2,6-methano-3-benzazocin-3(2H)-1-butanone; 4'-Fluoro-4-[1,4,5,6-tetrahydro-8-hydroxy-6,11-dimethyl-2,6-methano-3-benzazocin-3(2H)-yl]-butyrophenone
CAS No. 56390-16-0
项目整合开发状态: Biological Testing
项目研究机构: Sumitomo Pharmaceuticals (Originator)
合成路线:The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III),which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV).The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V),which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII).This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) ,which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX).Finally,this compound is hydrolyzed by refluxing with diluted aqueous HCl.
📄 详细内容
合成路线:The condensation of (VIII) with 3-(p-fluorobenzoyl)propionic acid (A) by means of ethyl chloroformate (B) and triethylamine in CHCl3 gives the corresponding N,O-diacyl derivative (X),which is then reduced with LiAlH4 in refluxing THF yielding 5,9-dimethyl-2-[4''-(p-fluorophenyl)4''-hydroxy-1''-butyl]-2'-hydroxy-5,9-dimethyl-6,7-benzomorphane (XI).Finally,this compound is oxidized with Jones reagent (H2CrO4 in H2SO4).
参考文献标题:Processes for producing 2-benzoylalkylbenzomorphan derivatives and their salts
文献作者:Atsumi,T.; et al.(Sumitomo Chemical Co.,Ltd.)
参考来源:DE 2114511; ES 389920; FR 2092005; GB 1311387
合成路线:The condensation of 3,4-dimethylpyridine (XV) with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) gives the corresponding pyridinium salt (XVII),which by reaction with p-methoxybenzylmagnesium chloride (I) in ether yields the dihydropyridine (XVIII).The reduction of (XVIII) with NaBH4 in methanol affords the tetrahydropyridine (XIX),which is finally cyclized by refluxing with AlBr3 in CS2; this reaction can also be performed by heating (XIX) with 48% aqueous HBr at 130 C.
参考文献标题:Preparation of 2-benzoylalkylbenzomorphan
文献作者:Atsumi,T.; et al.(Sumitomo Chemical Co.,Ltd.)
参考来源:DE 2128525; FR 2100743; GB 1329504; US 3953441
合成路线:The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III),which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV).The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V),which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII).This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) ,which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX).Finally,this compound is hydrolyzed by refluxing with diluted aqueous HCl.
合成路线:The condensation of (VIII) with 3-(p-fluorobenzoyl)propionic acid (A) by means of ethyl chloroformate (B) and triethylamine in CHCl3 gives the corresponding N,O-diacyl derivative (X),which is then reduced with LiAlH4 in refluxing THF yielding 5,9-dimethyl-2-[4''-(p-fluorophenyl)4''-hydroxy-1''-butyl]-2'-hydroxy-5,9-dimethyl-6,7-benzomorphane (XI).Finally,this compound is oxidized with Jones reagent (H2CrO4 in H2SO4).
合成路线:The nitration of 2,5,9-trimethyl-6,7-benzomorphane (XII) gives the 2'-nitro derivative (XIII),which by hydrogenation is converted into the corresponding 2'-amino compound (XIV).Finally,this compound is diazotized and converted into the hydroxy compound (V),already obtained.
合成路线:The condensation of 3,4-dimethylpyridine (XV) with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) gives the corresponding pyridinium salt (XVII),which by reaction with p-methoxybenzylmagnesium chloride (I) in ether yields the dihydropyridine (XVIII).The reduction of (XVIII) with NaBH4 in methanol affords the tetrahydropyridine (XIX),which is finally cyclized by refluxing with AlBr3 in CS2; this reaction can also be performed by heating (XIX) with 48% aqueous HBr at 130 C.
参考文献标题:ID-1229
文献作者:Castar,J.; Paton,D.M.
参考来源:Drugs Fut 1978,3(4),298
合成路线:The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III),which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV).The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V),which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII).This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) ,which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX).Finally,this compound is hydrolyzed by refluxing with diluted aqueous HCl.
参考文献标题:The synthesis and pharmacology of a new analgesic,ID-1229
文献作者:Yamamoto,H.; et al.
参考来源:Arzneim-Forsch Drug Res 1975,25(5),795-801
合成路线:The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III),which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV).The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V),which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII).This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) ,which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX).Finally,this compound is hydrolyzed by refluxing with diluted aqueous HCl.
参考文献标题:
文献作者:Atsumi,T.; et al.
参考来源:JP 7319314
合成路线:The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III),which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV).The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V),which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII).This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) ,which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX).Finally,this compound is hydrolyzed by refluxing with diluted aqueous HCl.
合成路线:The nitration of 2,5,9-trimethyl-6,7-benzomorphane (XII) gives the 2'-nitro derivative (XIII),which by hydrogenation is converted into the corresponding 2'-amino compound (XIV).Finally,this compound is diazotized and converted into the hydroxy compound (V),already obtained.
参考文献标题:
文献作者:Atsumi,T.; et al.
参考来源:JP 7343352