合成路线:The synthesis of [14C]-labeled tenidap sodium has been reported:The chlorination of [14C]-2,3-dihydro-1H-indole-2,3-dione (I) with sulfuryl chloride and triethylamine in hot acetonitrile gives the 5-chloro derivative (II),which is partially reduced by treatment with hydrazine hydrate in refluxing ethanol,followed by a treatment with KOH in the same refluxing solvent,to yield 5-chloro-2,3-dihydro-1H-indol-2-one (III).The reaction of (III) with chlorosulfonyl isocyanate (IV) in refluxing dichloromethane affords 5-chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (V),which is condensed with 2-thienylcarbonyl chloride (VI) by means of dimethylaminopyridine (DMAP) and triethylamine (TEA) in DMF,giving tenidap (VII).Finally,this compound is treated with NaHCO3 in hot acetone.
参考文献标题:Synthesis of C-14 isotopic isomers of tenidap - A novel antiinflammatory agent
文献作者:Johnson,D.L.; Melvin,L.S.; Falkner,F.C.; Rusek,F.W.; Robinson,R.P.
参考来源:J Label Compd Radiopharm 1996,38(3),207
合成路线:A new synthesis of tenidap has been developed:The reaction of 5-chloroindolin-2-one (I) with phenyl chloroformate and Et3N in THF gives 5-chloro-2-(phenoxycarbonyloxy)indole-1-carboxylic acid phenyl ester (II),which is treated with ammonium carbonate in DMF at 5 C yielding 5-chloro-2-oxoindoline-1-carboxylic acid phenyl ester (III).Compound (III) is acylated with 2-thienylcarbonyl chloride (IV) and DMAP in DMF and then acidified with conc.HCl affording 5-chloro-3-[1-hydroxy-1-(2-thienyl)methylene]-2-oxoindoline-1-carboxylic acid phenyl ester (V),which is finally treated with ammonium carbonate in DMF at 75-80 C for 5 h and acidified with conc.HCl.
参考文献标题:New practical synthesis of tenidap
文献作者:Siming,G.; Porcs-Makkay,M.
参考来源:Org Process Res Dev 2000,4(1),10
合成路线:5-Chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (X),a key intermediate in the synthesis of tenidap,has been obtained by several different ways,all of them starting from 5-chloro-2,3-dihydro-1H-indol-2-one (I).1.The reaction of indolone (I) with cyclohexylcarbonyl isocyanate (II) gives the N-acyl carboxamide (III),which is treated with KOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (IV).Finally,this compound is cyclized to the target carboxamide by treatment with trifluoroacetic anhydride and trifluoroacetic acid.2.The reaction of indolone (I) with isobutyryl isocyanate (XI) gives the N-acyl carboxamide (V),which is treated with KOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (III).Finally,this compound is cyclized to the target carboxamide as before.3.The reaction of indolone (I) with trichloroacetyl isocyanate (VI) in hot toluene gives the target carboxamide in one step.4.The reaction of indolone (I) with chlorosulfonyl isocyanate (VII) gives the N-chlorosulfonyl carboxamide (VIII),which is hydrolyzed to the target carboxamide with aqueous acetic acid.5.The reaction of indolone (I) with NaOH and then with H2SO4 gives 2-(2-amino-5-chlorophenyl)acetic acid (IX),which is treated with potassium isocyanate and AcOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (III).Finally,this compound can be cyclized to the target intermediate by means of AcOH and NaOAc.
参考文献标题:Synthesis of tenidap: An improved process for the preparation of 5-chloro-2-oxindole-1-carboxamide
文献作者:Sarma,M.R.; Goud,P.S.; Sailaja,M.; Kumar,P.R.; Reddy,G.O.; Raju,S.
参考来源:Org Process Res Dev 2001,5(1),61
合成路线:The synthesis of [14C]-labeled tenidap sodium has been reported:The chlorination of [14C]-2,3-dihydro-1H-indole-2,3-dione (I) with sulfuryl chloride and triethylamine in hot acetonitrile gives the 5-chloro derivative (II),which is partially reduced by treatment with hydrazine hydrate in refluxing ethanol,followed by a treatment with KOH in the same refluxing solvent,to yield 5-chloro-2,3-dihydro-1H-indol-2-one (III).The reaction of (III) with chlorosulfonyl isocyanate (IV) in refluxing dichloromethane affords 5-chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (V),which is condensed with 2-thienylcarbonyl chloride (VI) by means of dimethylaminopyridine (DMAP) and triethylamine (TEA) in DMF,giving tenidap (VII).Finally,this compound is treated with NaHCO3 in hot acetone.
参考文献标题:Asymmetric synthesis of the C17-C27 segment of the antineoplasticmacrolide bryostatin 1
文献作者:Hale,K.J.; Lennon,J.A.; Hobbs,C.J.; Javaid,M.H.; Manaviazar,S.
参考来源:J Label Compd Radiopharm 1995,36(8),1359
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