合成路线:1) The diazotation of 4-amino-N-methylbenzenemethanesulfonamide (I) with NaNO2-HCl followed by reduction with SnCl2 gives the 4-hydrazino compound (II),which is condensed with (phenylthio)acetaldehyde (III) in ethanol yielding the ethylideneamino compound (IV).The cyclization of (IV) with HCl in ethanol affords N-methyl-3-(phenylthio)-1H-indole-5-methansulfonamide (V),which is desulfurized with RaNi in refluxing ethanol-water to give N-methyl-1H-indole-5-methanesulfonamide (VI).The reaction of (VI) with oxalyl chloride and dimethylamine yields the oxalyl derivative (VII),which is finally reduced with LiAlH4 in refluxing THF.
合成路线:2) The condensation of hydrazine (II) with 4,4-dimethoxy-N,N-dimethylbutylamine (VIII) by means of HCl in water gives the butylidenehydrazino compound (IX),which is cyclized with polyphosphate ester (PPE) in CHCl3.
合成路线:3) The condensation of indole (VI) with N,N-diethylchloroacetamide (X) by means of POCl3 gives 3-chloroacetyl-N-methyl-1H-indole-5-methanesulfonamide (XI),which is treated with dimethylamine (XII) in refluxing ethanol to afford the dimethylaminoacetyl derivative (XIII),which is finally reduced with NaBH4 in refluxing propanol.
合成路线:4) The condensation of hydrazine (II) with 3-nitropropanal (XIV) in water gives the nitrobutylidenehydrazino derivative (XV),which is cyclized with PPE as before yielding N-methyl-3-(2-nitroethyl)-1H-indole-5-methansulfonamide (XVI),which is reduced with H2 over Pd/C in ethyl acetate to afford the 2-aminoethyl compound (XVII).Finally,this compound is methylated with ICH3 and NaHCO3 or with formaldehyde and NaBH4
合成路线:5) The condensation of hydrazino compound (II) with 4,4-dimethoxybutyronitrile (XVIII) gives the cyanobutylideneamino derivative (XIX),which is cyclized with PPE as before yielding 3-(cyanomethyl)-N-methyl-1H-indole-5-methanesulfonamide (XX).Finally,this compound is reduced with H2 over Rh/Al2O3 to afford the 2-aminoethyl derivative (XVII),already obtained.
参考文献标题:Heterocyclic compounds.
文献作者:Coates,I.H.; Dowle,M.D.(Glaxo Group Ltd.)
参考来源:FR 2530625; GB 2124210; US 4816470
合成路线:1) The diazotation of 4-amino-N-methylbenzenemethanesulfonamide (I) with NaNO2-HCl followed by reduction with SnCl2 gives the 4-hydrazino compound (II),which is condensed with (phenylthio)acetaldehyde (III) in ethanol yielding the ethylideneamino compound (IV).The cyclization of (IV) with HCl in ethanol affords N-methyl-3-(phenylthio)-1H-indole-5-methansulfonamide (V),which is desulfurized with RaNi in refluxing ethanol-water to give N-methyl-1H-indole-5-methanesulfonamide (VI).The reaction of (VI) with oxalyl chloride and dimethylamine yields the oxalyl derivative (VII),which is finally reduced with LiAlH4 in refluxing THF.
合成路线:2) The condensation of hydrazine (II) with 4,4-dimethoxy-N,N-dimethylbutylamine (VIII) by means of HCl in water gives the butylidenehydrazino compound (IX),which is cyclized with polyphosphate ester (PPE) in CHCl3.
合成路线:3) The condensation of indole (VI) with N,N-diethylchloroacetamide (X) by means of POCl3 gives 3-chloroacetyl-N-methyl-1H-indole-5-methanesulfonamide (XI),which is treated with dimethylamine (XII) in refluxing ethanol to afford the dimethylaminoacetyl derivative (XIII),which is finally reduced with NaBH4 in refluxing propanol.
合成路线:4) The condensation of hydrazine (II) with 3-nitropropanal (XIV) in water gives the nitrobutylidenehydrazino derivative (XV),which is cyclized with PPE as before yielding N-methyl-3-(2-nitroethyl)-1H-indole-5-methansulfonamide (XVI),which is reduced with H2 over Pd/C in ethyl acetate to afford the 2-aminoethyl compound (XVII).Finally,this compound is methylated with ICH3 and NaHCO3 or with formaldehyde and NaBH4
合成路线:5) The condensation of hydrazino compound (II) with 4,4-dimethoxybutyronitrile (XVIII) gives the cyanobutylideneamino derivative (XIX),which is cyclized with PPE as before yielding 3-(cyanomethyl)-N-methyl-1H-indole-5-methanesulfonamide (XX).Finally,this compound is reduced with H2 over Rh/Al2O3 to afford the 2-aminoethyl derivative (XVII),already obtained.
参考文献标题:An indole derivative.
文献作者:Oxford,A.W.(Glaxo Group Ltd.)
参考来源:GB 2162522
产品链接: CAS No. 103628-48-4›› 产品链接: CAS No.103628-46-2››