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Enpiroline, WR-180409(phosphate)

恩哌罗林Chemical Name: threo-alpha-(2-Piperidyl)-2-trifluoromethyl-6-(4-trifluoromethylphenyl)-4-pirdinemethanol
CAS No. 66364-73-6, 66364-74-7 (phosphate), 52300-95-5 (threo-isomer)
项目整合开发状态: Phase III
项目研究机构: Walter Reed Army Institute (Originator)
合成路线:The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III),which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V).Finally,this compound is reduced with H2 over Pt in aqueous concentrated HCl.The starting products are prepared as follows:1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether.An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C.2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI),which is then condensed with pyridine.
📌 参考资料/链接:
参考文献标题:2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials
文献作者:Ash,A.B.; et al.(Department of the Army)
参考来源:US 3886167

📄 详细内容


合成路线:The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III),which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V).Finally,this compound is reduced with H2 over Pt in aqueous concentrated HCl.The starting products are prepared as follows:1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether.An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C.2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI),which is then condensed with pyridine.

参考文献标题:2-Substituted phenyl-6-trifluoromethyl-4-pyridylcarbinolamines
文献作者:Ash,A.B.; et al.(Department of the Army)
参考来源:US 3940404


合成路线:The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III),which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V).Finally,this compound is reduced with H2 over Pt in aqueous concentrated HCl.The starting products are prepared as follows:1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether.An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C.2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI),which is then condensed with pyridine.

参考文献标题:2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials
文献作者:Ash,A.B.; et al.(Department of the Army)
参考来源:US 3953463


合成路线:The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III),which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V).Finally,this compound is reduced with H2 over Pt in aqueous concentrated HCl.The starting products are prepared as follows:1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether.An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C.2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI),which is then condensed with pyridine.

参考文献标题:WR-180,409
文献作者:Castar,J.; Roberts,P.J.
参考来源:Drugs Fut 1978,3(9),694


合成路线:The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III),which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V).Finally,this compound is reduced with H2 over Pt in aqueous concentrated HCl.The starting products are prepared as follows:1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether.An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C.2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI),which is then condensed with pyridine.
参考文献标题:Antimalarials.6.Synthesis,antimalarial activity and configurations of rracemic alpha-(2-piperidyl)-4-pyridinemethanols
文献作者:La Montagne,M.P.; et al.
参考来源:J Med Chem 1974,17(5),219-523


产品链接: CAS No. 66364-73-6››

产品链接: CAS No.66364-74-7››