合成路线:The chlorination of 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine-N-oxide (I) with trichloroisocyanuric acid in hot chloroform gives the 2-chloromethyl derivative (II),which is condensed with 2-mercapto-1H-benzimidazole (III) by means of NaOH in methanol to yield the adduct (IV).The reaction of (IV) with PCl3 and acetic acid eliminates the N-oxide group,affording the sulfanylmethylpyridine (V).Finally,this compound is oxidized with tert-butyl hydroperoxide (VI) in ethanol to provide the target sulfoxide.Alternatively,the intermediate adduct (IV) can also be obtained as follows: The chlorination of 2,3-dimethyl-4-nitropyridine-N-oxide (VII) with trichloroisocyanuric acid as before gives the chloromethyl derivative (VIII),which is condensed with 2-mercapto-1H-benzimidazole (III) as before to yield the adduct (IX).Finally,this compound is treated with 2,2,2-trifluoroethanol (X),benzyltrimethylammonium chloride and K2CO3 in acetonitrile to afford the target intermediate (IV).
参考文献标题:Intermediate for the synthesis of lansoprazole and process for obtaining it
文献作者:Montserrat Vidal,C.; Serra Macia,X.(Laboratorios Salvat SA)
参考来源:ES 2063705
合成路线:The condensation of 2,3-dimethyl-4-nitropyridine N-oxide (I) with 2,2,2-trifluoroethanol (II) by means of K2CO3 in hot HMPT gives 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine N-oxide (III),which by isomerization in acetic anhydride at 100 C is converted to 2-(hydroxymethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine (IV).The reaction of (IV) with SOCl2 in refluxing CHCl3 affords the corresponding chloromethyl derivative (V),which is condensed with 2-mercaptobenzimidazole (VI) by means of sodium methoxide in refluxing methanol to yield 2-(2-benzimidazolylthiomethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridin (VII).Finally,this compound is oxidized with m-chloroperbenzoic acid in CHCl3.
参考文献标题:LANSOPRAZOLE < Prop INN >
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(7),625
合成路线:The condensation of 2,3-dimethyl-4-nitropyridine N-oxide (I) with 2,2,2-trifluoroethanol (II) by means of K2CO3 in hot HMPT gives 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine N-oxide (III),which by isomerization in acetic anhydride at 100 C is converted to 2-(hydroxymethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine (IV).The reaction of (IV) with SOCl2 in refluxing CHCl3 affords the corresponding chloromethyl derivative (V),which is condensed with 2-mercaptobenzimidazole (VI) by means of sodium methoxide in refluxing methanol to yield 2-(2-benzimidazolylthiomethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridin (VII).Finally,this compound is oxidized with m-chloroperbenzoic acid in CHCl3.
参考文献标题:Stabilized pharmaceutical composition comprising a benzimidazole compound,its production and its use as an antiulcer agent.
文献作者:Makino,T.; Tabata,T.; Hirai,S.
参考来源:EP 237200; JP 87277322
产品链接: CAS No. 103577-45-3››