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Fludarabine, NSC-118218, 2-F-ara-A

氟达拉滨Chemical Name: 9-(beta-D-Arabinofuranosyl)-2-fluoro-9H-purin-6-amine; 9-(beta-D-Arabinofuranosyl)-2-fluoroadenine
CAS No. 21679-14-1
项目整合开发状态: Not Determined
项目研究机构:
合成路线:This compound can be obtained by two different ways:1) The cyclization of 2,4,5,6-tetraaminopyrimidine (I) with refluxing formamide (II) gives 2-aminoadenine (III),which is acetylated by treatment with acetic anhydride in refluxing pyridine to yield 2,6-diacetamidopurine (IV).The condensation of (IV) with 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose (V) by treatment with HCl in CH2Cl2 affords 2-amino-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)adenine (VI) which is fluorinated by reaction with HBF4 in THF giving 9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine (VII).Finally this compound is debenzylated by treatment with BCl3 in CH2Cl2 or with Na in liquid NH3.

合成路线:2) The condensation of 2,6-dichloropurine (VIII) with 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride (IX) by means of Hg(CN)2 in CH2Cl2 gives 9-(2,3,5-tri-O-benzyl-D-arabinofuranosyl)-2,6-dichloropurine (X),which is treated with NaN3 in refluxing ethanol - water to yield 2,6-diazido-9-(2,3,6-tri-O-benzyl-D-arabinofuranosyl)purine (XI).Finally this compound is reduced with H2 over Pd/C in ethanol to afford adenine (VI).
📌 参考资料/链接:
参考文献标题:F-ARA-A
文献作者:Blancafort,P.; Serradell,M.N.; Castar,J.; Hopkins,S.J.
参考来源:Drugs Fut 1982,7(8),561

📄 详细内容


合成路线:This compound can be obtained by two different ways:1) The cyclization of 2,4,5,6-tetraaminopyrimidine (I) with refluxing formamide (II) gives 2-aminoadenine (III),which is acetylated by treatment with acetic anhydride in refluxing pyridine to yield 2,6-diacetamidopurine (IV).The condensation of (IV) with 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose (V) by treatment with HCl in CH2Cl2 affords 2-amino-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)adenine (VI) which is fluorinated by reaction with HBF4 in THF giving 9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine (VII).Finally this compound is debenzylated by treatment with BCl3 in CH2Cl2 or with Na in liquid NH3.

参考文献标题:
文献作者:Montgomery,J.A.
参考来源:US 4210745


合成路线:2) The condensation of 2,6-dichloropurine (VIII) with 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride (IX) by means of Hg(CN)2 in CH2Cl2 gives 9-(2,3,5-tri-O-benzyl-D-arabinofuranosyl)-2,6-dichloropurine (X),which is treated with NaN3 in refluxing ethanol - water to yield 2,6-diazido-9-(2,3,6-tri-O-benzyl-D-arabinofuranosyl)purine (XI).Finally this compound is reduced with H2 over Pd/C in ethanol to afford adenine (VI).

参考文献标题:
文献作者:Montgomery,J.A.
参考来源:US 4188378


合成路线:This compound can be obtained by two different ways:1) The cyclization of 2,4,5,6-tetraaminopyrimidine (I) with refluxing formamide (II) gives 2-aminoadenine (III),which is acetylated by treatment with acetic anhydride in refluxing pyridine to yield 2,6-diacetamidopurine (IV).The condensation of (IV) with 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose (V) by treatment with HCl in CH2Cl2 affords 2-amino-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)adenine (VI) which is fluorinated by reaction with HBF4 in THF giving 9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine (VII).Finally this compound is debenzylated by treatment with BCl3 in CH2Cl2 or with Na in liquid NH3.

参考文献标题:An improved procedure for the preparation of 9-B-D-arabinofuranosyl-2-fluoroadenine
文献作者:Montgomery,J.A.; Clayton,S.D.; Shortnacy,A.T.
参考来源:J Heterocycl Chem 1979,16(1),157-160


合成路线:2) The condensation of 2,6-dichloropurine (VIII) with 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride (IX) by means of Hg(CN)2 in CH2Cl2 gives 9-(2,3,5-tri-O-benzyl-D-arabinofuranosyl)-2,6-dichloropurine (X),which is treated with NaN3 in refluxing ethanol - water to yield 2,6-diazido-9-(2,3,6-tri-O-benzyl-D-arabinofuranosyl)purine (XI).Finally this compound is reduced with H2 over Pd/C in ethanol to afford adenine (VI).
参考文献标题:Nucleosides of 2-fluoroadenine
文献作者:Montgomery,J.A.; Hewson,K.
参考来源:J Med Chem 1969,12498-504


产品链接: CAS No. 21679-14-1››