Almotriptan, PNU-180638, LAS-31416, Almogran, Axert

合成路线:Almotriptan has been obtained by several related ways:1) The hydrolysis of 4-chlorobutyraldehyde dimethylacetal (I) with HCl gives the corresponding aldehyde (II),which is condensed with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in methanol/water,giving 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV).Finally,this compound is methylated with formaldehyde and NaBH4 in methanol.2) The direct condensation of 4-chlorobutyraldehyde dimethylacetal (I) with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in water also yields intermediate 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV).3) The decarboxylation of 3-[2-(dimethylamino)ethyl]-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole-2-carboxylic acid (V) catalyzed by means of Cu2O in quinoline at 190 C also gives almotriptan.

参考文献标题:Process for the preparation of indole derivs.
文献作者:Fern醤dez Forner,M.D.; Puig Dur醤,C.; Crespo Crespo,M.I.; Moragues Mauri,J.(Almirall Prodesfarma,SA)
参考来源:ES 2084560


合成路线:Almotriptan has been obtained by several related ways:1) The hydrolysis of 4-chlorobutyraldehyde dimethylacetal (I) with HCl gives the corresponding aldehyde (II),which is condensed with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in methanol/water,giving 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV).Finally,this compound is methylated with formaldehyde and NaBH4 in methanol.2) The direct condensation of 4-chlorobutyraldehyde dimethylacetal (I) with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in water also yields intermediate 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV).3) The decarboxylation of 3-[2-(dimethylamino)ethyl]-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole-2-carboxylic acid (V) catalyzed by means of Cu2O in quinoline at 190 C also gives almotriptan.

参考文献标题:New indole derivs.
文献作者:Pujol Noguera,F.; Crespo Crespo,M.I.; Puig Dur醤,C.; Fern醤dez Forner,D.; Moragues Mauri,J.(Almirall Prodesfarma,SA)
参考来源:ES 2056025


合成路线:4) The intermediate 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) can be obtained as follows: The condensation of pyrrolidine (VI) with 1-(4-nitrobenzylsulfonyl)chloride (VII) in dichloromethane gives the expected sulfonamide (VIII),which is reduced with H2 over RaNi in DMF,yielding 4-(1-pyrrolidinylsulfonylmethyl)aniline (IX).The diazotation of (IX) with NaNO2/HCl affords the corresponding diazo compound (X),which is finally reduced to the target intermediate (III) with SnCl2/HCl.
参考文献标题:New aniline derivatives as key intermediates in th
文献作者:Fernandez-Forner,D.
参考来源:Res Disclosure 1998,4121088


产品链接: CAS No. 154323-57-6››