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Dantrolene sodium, F-440, Dantrium

丹曲林钠 1-(((5-(4-硝基苯基)呋喃-2-基)亚甲基)氨基)咪唑烷-2,4-二酮 Chemical Name: 1-[5-(4-Nitrophenyl)furfurylideneamino]hydantoin sodium salt
CAS No. 14663-23-1, 7261-97-4 (free acid)
项目整合开发状态: Launched-1971
项目研究机构: Procter & Gamble (Originator)
合成路线:In an alternative method,condensation of semicarbazide hydrochloride (I) with cyclohexanone (II) yields the semicarbazone (III).Subsequent reaction of (III) with ethyl chloroacetate (IV) in the presence of NaOMe gives rise to the cyclohexylidene aminohydantoin (V).Treatment of (V) with 5-(p-nitrophenyl)furfural (VI) under acidic conditions affords the furfurylidene aminohydantoin (VII).This is finally converted into the corresponding sodium salt employing methanolic NaOMe (3).
📌 参考资料/链接:
参考文献标题:Process for obtaining 1-[(5-(p-nitrophenyl)furfuryliden)amino]hydantoin and its sodium salt
文献作者:Martin-Escudero Perez,U.; Izquierdo Sanjose,M.
参考来源:ES 458000

📄 详细内容


合成路线:The title compound has also been obtained by solid phase synthesis.Bromoacetic acid (I) is coupled to hydroxymethyl polystyrene resin by means of DIC/DMAP to produce the bromoacetyl resin (II).Bromide displacement with tert-butyl carbazate (III) leads to the N-Boc hydrazino ester (IV),which is further deprotected to (V) employing trifluoroacetic acid.The hydrazinoacetic acid-bound resin (V) is then condensed with 5-(p-nitrophenyl)furfural (VI) to furnish hydrazone (VII).Acylation of resin (VII) with p-nitrophenyl chloroformate (VIII) produces the p-nitrophenyl carbamate (IX),which upon treatment with ammonia gives rise to the semicarbazone (X).Finally,concomitant intramolecular ring closure and resin cleavage of (X) produces the target aminohydantoin derivative (XI) (4,5).

参考文献标题:Solid phase synthesis of 1-aminohydantoins
文献作者:Portlock,D.E.; Li,M.; Wilson,L.J.(The Procter & Gamble Co.)
参考来源:WO 9942450


合成路线:Diazotization of 4-nitroaniline (I),followed by copper-catalyzed coupling of the resultant diazonium salt (II) with 2-furaldehyde (III) leads to 5-(p-nitrophenyl)-2-furancarboxaldehyde (IV) (1).Cyclization of semicarbazideacetic acid (V) by heating in aqueous sulfuric acid leads to 1-aminohydantoin (VI) (2).This is then condensed with aldehyde (IV) to furnish the furfurylidene aminohydantoin (VII) (1,2).Treatment of (VII) with sodium methoxide gives rise to the corresponding sodium salt (1).

参考文献标题:1-[(5-Arylfurfurylidene)amino]hydantoins.A new class of muscle relaxants
文献作者:Snyder,H.R.Jr.; Davis,C.S.; Bickerton,R.K.; Halliday,R.P.
参考来源:J Med Chem 1967,10(5),807


合成路线:Diazotization of 4-nitroaniline (I),followed by copper-catalyzed coupling of the resultant diazonium salt (II) with 2-furaldehyde (III) leads to 5-(p-nitrophenyl)-2-furancarboxaldehyde (IV) (1).Cyclization of semicarbazideacetic acid (V) by heating in aqueous sulfuric acid leads to 1-aminohydantoin (VI) (2).This is then condensed with aldehyde (IV) to furnish the furfurylidene aminohydantoin (VII) (1,2).Treatment of (VII) with sodium methoxide gives rise to the corresponding sodium salt (1).

参考文献标题:Furan derivatives.XXIII.Synthesis and absorption spectra of 5-(nitrophenyl)-2-furaldehyde derivatives
文献作者:Frimm,R.; Kovac,S.; Giller,S.A.
参考来源:Chem Zvesti 1969,23(11-12),916


合成路线:The title compound has also been obtained by solid phase synthesis.Bromoacetic acid (I) is coupled to hydroxymethyl polystyrene resin by means of DIC/DMAP to produce the bromoacetyl resin (II).Bromide displacement with tert-butyl carbazate (III) leads to the N-Boc hydrazino ester (IV),which is further deprotected to (V) employing trifluoroacetic acid.The hydrazinoacetic acid-bound resin (V) is then condensed with 5-(p-nitrophenyl)furfural (VI) to furnish hydrazone (VII).Acylation of resin (VII) with p-nitrophenyl chloroformate (VIII) produces the p-nitrophenyl carbamate (IX),which upon treatment with ammonia gives rise to the semicarbazone (X).Finally,concomitant intramolecular ring closure and resin cleavage of (X) produces the target aminohydantoin derivative (XI) (4,5).
参考文献标题:Solid phase synthesis of 1-aminohydantoin libraries
文献作者:Wilson,L.J.; Li,M.; Portlock,D.E.
参考来源:Tetrahedron Lett 1998,39(29),5135


产品链接: CAS No. 14663-23-1››

产品链接: CAS No.7261-97-4››