合成路线:A new method for the synthesis of sorbinil has been reported:The condensation of 2,3-dihydro-6-fluoro-4H-1-benzopyran-4-one (I) with methylbenzylamine (II) by means of TiCl4 in benzene gives 2,3-dihydro-6-fluoro-4-(1-phenylethylimino)-4H-1-benzopyran (III),which by reaction with HCN in ethanol is converted to 4-cyano-2,3-dihydro-6-fluoro-4-(1-phenylethylamino)-4H-1-benzopyran (IV).The cyclization of (IV) with chlorosulfonyl isocyanate (V) in methylene chloride affords 2,3-dihydro-6-fluoro-3'-(1-phenylethyl)spiro(4H-1-benzopyran-4,4'-imidazolidine)-2',5'-dione (VI),which is finally treated with 48% HBr in refluxing acetic acid.
参考文献标题:Intermediates in the preparation of chiral hydantoins
文献作者:Sarges,R.(Pfizer Inc.)
参考来源:US 4348526
合成路线:The cyclization of 3-(p-fluorophenoxy)propionic acid (I) with polyphosphoric acid in boiling water gives 6-fluoro-4-chromanone (II),which is then treated with KCN and ammonium carbonate in hot ethanol-water.
参考文献标题:Sorbinil
文献作者:Castar,J.; Sweetman,A.J.
参考来源:Drugs Fut 1980,5(4),204
合成路线:The condensation of 4-fluorophenol (I) with 1,2-dibromoethane (II) in basic medium gives 2-(4-fluorophenyl)ethyl bromide (III),which by reaction with N-benzoyl-2-hydroxyglycine (IV) in methanesulfonic acid yields N-benzoyl-2-[2-(2-bromoethoxy)-5-fluorophenyl]glycine (V).The cyclization of (V) with acetic anhydride and triethylamine at 50 C affords 6-fluoro-2'-phenylspiro[2,3-dihydro-4H-1-benzopyran-4,4'-oxazolidine]-5'-one (VI),which is hydrolyzed with refluxing formic acid-HCl giving the amino acid (VII).The esterification of (VII) with SOCl2 and methanol in the usual way yields the methyl ester (VIII),which is submitted to optical resolution by selective hydrolysis with alpha-chymotrypsine affording methyl 4(S)-amino-6-fluoro-2,3-dihydro-4H-1-benzopyrano-4-carboxylate (IX).Finally,this compound is converted into sorbinil by cyclization with sodium cyanate in acetic acid at room temperature.
参考文献标题:Novel synthesis of the aldose reductase inhibitor sorbinil via amidoalkylation,intramolecular oxazolidin-5-one alkylation,and chymotrypsin resolution
文献作者:Dirlam,N.L.; Moore,B.S.; Urban,F.J.
参考来源:J Org Chem 1987,52(16),3587-91
合成路线:The synthesis of [2H]-,[3H]- and [14C]-radiolabeled sorbinil has been described:[2H]- and [3H]-sorbinil are prepared by chlorination of sorbinil (I) with Cl2 and FeCl2 in dry DMF to give the 8-chloro derivative (II),which is then reduced with deuterium or tritium over Pd/C in ethanol.[14C]-Labeled sorbinil is prepared by cyclization of 6-fluoro-3,4-dihydro-2H-benzo[b]pyran-4-one (III) with [14C]-potassium cyanide and ammonium carbonate in hot ethanol-water to give radiolabeled racemic sorbinil,which is then submitted to optical resolution with brucine in ethanol.
参考文献标题:Synthesis of H-2-labelled,H-3-labelled and C-14-labelled CP-45,634 (sorbinil)
文献作者:Howard,H.R.; Sarges,R.; Evans,M.
参考来源:J Label Compd Radiopharm 1991,29(6),703
合成路线:The cyclization of 3-(p-fluorophenoxy)propionic acid (I) with polyphosphoric acid in boiling water gives 6-fluoro-4-chromanone (II),which is then treated with KCN and ammonium carbonate in hot ethanol-water.
参考文献标题:
文献作者:
参考来源:BE 0867248
合成路线:A new method for the synthesis of sorbinil has been reported:The condensation of 2,3-dihydro-6-fluoro-4H-1-benzopyran-4-one (I) with methylbenzylamine (II) by means of TiCl4 in benzene gives 2,3-dihydro-6-fluoro-4-(1-phenylethylimino)-4H-1-benzopyran (III),which by reaction with HCN in ethanol is converted to 4-cyano-2,3-dihydro-6-fluoro-4-(1-phenylethylamino)-4H-1-benzopyran (IV).The cyclization of (IV) with chlorosulfonyl isocyanate (V) in methylene chloride affords 2,3-dihydro-6-fluoro-3'-(1-phenylethyl)spiro(4H-1-benzopyran-4,4'-imidazolidine)-2',5'-dione (VI),which is finally treated with 48% HBr in refluxing acetic acid.
参考文献标题:Synthesis of optically active spirohydantoins by asymmetric induction.Hydantoin formation from amino nitriles and chlorosulfonyl isocyanate
文献作者:Kelbaugh,P.R.; Sarges,R.; Howard,H.R.Jr.
参考来源:J Org Chem 1982,47(21),4081-85
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