合成路线:This compound can be prepared in two different ways:1) The reaction of alpha-trifluoromethylacrylonitrile (I) with HBr in ethanol gives alpha-trifluoromethyl-beta-bromopropionamide (II),which is condensed with acetylurea (A) in hot aqueous dioxane to yield alpha-trifluoromethyl-beta-(N-acetylureido)propionamide (III).The cyclization of (III) with aqueous HCl at 120 C affords 5,6-dihydro-5-trifluoromethyluracil (IV),which is brominated with Br2 in refluxing acetic acid to afford 5,6-dihydro-5-bromo-5-trifluoromethyluracil (V).The dehydrobromination of (V) in DMF at 135-45 C gives 5-trifluoromethyluracil (VI),which is condensed with 2-deoxy-alpha-D-ribose-1-phosphate (VII) by means of a nucleosidephosphorylase preparation,or an exchange reaction with thymidine catalyzed by an enzyme3 obtained from Escherichia Coli B.2) The reaction of 5-trifluoromethyluracil (VI) with trimethylchlorosilane in refluxing hexamethyldisilazane gives bis(trimethylsilyl)-5-trifluoromethyluracil (VIII),which is condensed with 3,5-bis(O-p-nitrobenzoyl)-1,2-dideoxy-1-chloro-D-ribofuranose (IX) by means of mercuric acetate in benzene to afford 3',5'-bis-O-(p-nitrobenzoyl)-2'-deoxy-5-trifluoromethyluridine (X).Finally,this compound is hydrolyzed by treatment with diisopropylamine in refluxing methanol.
参考文献标题:
文献作者:Ryan,K.J.; et al.
参考来源:US 3531464
合成路线:This compound can be prepared in two different ways:1) The reaction of alpha-trifluoromethylacrylonitrile (I) with HBr in ethanol gives alpha-trifluoromethyl-beta-bromopropionamide (II),which is condensed with acetylurea (A) in hot aqueous dioxane to yield alpha-trifluoromethyl-beta-(N-acetylureido)propionamide (III).The cyclization of (III) with aqueous HCl at 120 C affords 5,6-dihydro-5-trifluoromethyluracil (IV),which is brominated with Br2 in refluxing acetic acid to afford 5,6-dihydro-5-bromo-5-trifluoromethyluracil (V).The dehydrobromination of (V) in DMF at 135-45 C gives 5-trifluoromethyluracil (VI),which is condensed with 2-deoxy-alpha-D-ribose-1-phosphate (VII) by means of a nucleosidephosphorylase preparation,or an exchange reaction with thymidine catalyzed by an enzyme3 obtained from Escherichia Coli B.2) The reaction of 5-trifluoromethyluracil (VI) with trimethylchlorosilane in refluxing hexamethyldisilazane gives bis(trimethylsilyl)-5-trifluoromethyluracil (VIII),which is condensed with 3,5-bis(O-p-nitrobenzoyl)-1,2-dideoxy-1-chloro-D-ribofuranose (IX) by means of mercuric acetate in benzene to afford 3',5'-bis-O-(p-nitrobenzoyl)-2'-deoxy-5-trifluoromethyluridine (X).Finally,this compound is hydrolyzed by treatment with diisopropylamine in refluxing methanol.
参考文献标题:Trifluridine
文献作者:Castar,J.; Blancafort,P.; Hopkins,S.J.; Serradell,M.N.
参考来源:Drugs Fut 1980,5(11),561
产品链接: CAS No. 70-00-8››