合成路线:A new synthesis of pergolide has been reported:The alkylation of 8,9-dihydroelymoclavine (I) with propyl iodide and Na2CO3 in N-methylpyrrolidone gives the quaternary compound (II),which is mesylated with MeSO2Cl in pyridine yielding the mesyl ester (III).Finally,(III) is treated with sodium methylmercaptide in N-methylpyrrolidone.
参考文献标题:One-pot process for preparing pergolide
文献作者:Misner,J.W.(Eli Lilly and Company)
参考来源:EP 0571202
合成路线:The reaction of methyl dihydro-lysergate (I) with cyanogen bromide in methylene chloride gives 6-cyano-8beta-methoxycarbonylergoline (II),which is treated with Zn dust and acetic acid - water to afford 8beta-methoxycarbonylergoline (III).The alkylation of (III) with propyl bromide (A) and potassium carbonate in DMF yields 6-n-propyl-8beta-methoxycarbonylergoline (IV),which is reduced with NaBH4 in dioxane - methanol to 6-n-propyl-8beta-hydroxymethylergoline (V).The mesylation of (V) with mesyl chloride in pyridine gives 6-n-propyl-8beta-mesyloxymethylergoline (VI),which is finally treated with sodium methylmercaptide in dimethylacetamide and with methanesulfonic acid.
参考文献标题:Pergolide mesylate
文献作者:Serradell,M.N.; Castar,J.; Blancafort,P.; Owen,R.T.
参考来源:Drugs Fut 1981,6(4),231
合成路线:A new synthesis of pergolide has been reported:The alkylation of 8,9-dihydroelymoclavine (I) with propyl iodide and Na2CO3 in N-methylpyrrolidone gives the quaternary compound (II),which is mesylated with MeSO2Cl in pyridine yielding the mesyl ester (III).Finally,(III) is treated with sodium methylmercaptide in N-methylpyrrolidone.
合成路线:The reaction of dihydrolysergol (I) with BrCN in DMF gives the N-cyano derivative (II),which is treated with NaOH in ethylene glycol yielding the demethylated compound (III).The reductive alkylation of (III) with propionaldehyde (IV) and formic acid in DMF affords the propyl derivative (V),which is mesylated with MsCl and pyridine giving the mesylate (VI).Finally,this compound is treated with sodium methylthiolate and MsOH.
参考文献标题:Integration of a highly selective demethylation of a qaternized ergoline into a one-pot synthesis of pergolide
文献作者:Misner,J.W.; et al.
参考来源:Org Process Res Dev 1997,1(1),77
合成路线:The reaction of dihydrolysergol (I) with propyl iodide (II) in hot sulfolane gives the quaternary salt (III),which is treated with Na2S in the same solvent,yielding the propyl derivative (IV).The reaction of (IV) with mesyl chloride and pyridine affords the corresponding mesylate (V),which is finally treated with commercial Na-S-CH3 in DMF to afford the target methylsulfanyl derivative.
参考文献标题:Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethylation with sodium sulfide or potassium thioacetate: An application to the synthesis of pergolide
文献作者:Anastasia,L.; et al.
参考来源:J Chem Soc - Perkins Trans I 2001,(19),2398
产品链接: CAS No. 66104-23-2›› 产品链接: CAS No.66104-22-1››