Drofenine | 94676-97-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Drofenine
• 英文别名: dicyclohexyl-acetic acid-(2-diethylamino-ethyl ester)；Dicyclohexyl-essigsaeure-(2-diaethylamino-aethylester)；2-(Diethylamino)ethyl 2,2-dicyclohexylacetate；2-(diethylamino)ethyl 2,2-dicyclohexylacetate
• CAS: 94676-97-8
• 化学式: C₂₀H₃₇NO₂
• 分子量: 323.519
• InChiKey: NTMDEZKGNINQSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溴甲烷 、 Drofenine 在 乙酸乙酯 作用下， 生成 diethyl-(2-dicyclohexylacetoxy-ethyl)-methyl-ammonium; bromide
  参考文献：
  名称：

  Basic esters and process of preparing same

  摘要：

  532,943. 二取代脂肪酸的烷胺酯。巴塞尔化学工业协会。1939年8月1日，编号22277和22278。会议日期，1938年8月5日和1939年6月20日。[2（iii）类]二脂环或芳基脂环脂肪酸与氨基醇在氨基上取代的酯转化为它们的酯。因此，脂肪酸或其反应衍生物，如卤化物、酯、酸酐或酮，与氨基醇反应；或者氨基醇的反应酯与脂肪酸或其盐反应；或者脂肪酸或其反应衍生物可以与含有取代基（例如卤素）的醇结合，然后通过与胺作用替换为取代的氨基。这些在治疗上有用的产品可以转化为它们的季铵盐。根据示例，（1）二环己基乙酸2-二乙基氨基乙醇酯是通过将酸氯与氨基醇反应制备的，该酸氯是通过用亚砜氯制备的酸制备的；它的溴甲基酸酯通过与溴代烷反应形成，其溴甲基酸酯、溴乙酸酯和溴苄酸酯类似制备；（2）苯基环己基乙酸与氯乙基二乙胺在存在或不存在碳酸钾的情况下加热，得到二乙基氨基乙醇酯，可以通过与溴甲烷处理转化为其溴甲基酸酯；苯基环己基丙酸、苯基-环己基-丁酸、二环戊基乙酸、苯基-环戊基-乙酸、苯基-#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环己基-乙酸和苯基-#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环戊烯基-乙酸的相同酯也类似获得；还有苯基环己基乙酸的哌啶-乙醇、二乙基氨基正丁醇、二乙基氨基乙醇、吗啉-乙醇、乙基-乙酰氧乙基氨基乙醇、乙基-羟丙基氨基乙醇、甲基-丙基氨基乙醇和苯基环己基乙酸的m-二甲基氨基环己醇酯。还提到以下额外的酯：二环己基乙酸曲马多酯，α:α<;SP>;1<;/SP>;-二环己基-α-羟基乙酸二乙基氨基乙醇酯，α-苯基-α-环己基-α-羟基乙酸二乙基氨基乙醇酯，苯基-环己基乙酸酯的可卡因甲酯和苯基二甲基氨基环己基乙酸二乙基氨基乙醇酯。根据第91节开放检查的规范还描述了单脂环脂肪酸的烷胺酯的制备。因此，通过在铂存在下用氢还原苯乙酸制备环己基乙酸，将其氯化为环己基乙酸二乙基氨基乙醇酯。类似地，α-环己基羟基丙酸曲马多和斯科平酯（该酸通过在铂存在下用氢还原曲马酸制备）；α-环己基-α-丙基乙酸二乙基氨基乙醇酯（该酸通过在铂存在下用氢还原α-苯基-α-丙基乙酸制备），以及环己基-二乙基氨基乙基乙酸二乙基氨基乙醇酯（该酸通过苯乙腈与二乙基氨基乙基氯在苏打胺存在下反应，腈的皂化和产物的还原制备）。其他可能使用的酸是环己烯基脂肪酸和氢化萘脂肪酸。这个主题在接受的规范中没有出现。二脂环和芳基脂环脂肪酸。苯基环己基乙酸是通过苯乙腈与环己基溴在苏打胺存在下反应并皂化产物制备的。类似地，通过苯乙腈与A ，-或A 2-环己烯基溴、#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环戊烯基溴或二甲基氨基环己基溴反应，然后皂化，得到相应的二取代乙酸。苯基环己基丙酸和-丁酸是通过在镍催化剂存在下用氢还原二苯基-丙酸或-丁酸酯，然后皂化酯制备的。苯基环戊基乙酸是通过温和还原剂作用于苯基环戊烯基乙酸制备的。α:α-二环己基-α-羟基乙酸是通过苯甲酸酮催化还原得到的。α-苯基-x-环己基-α-羟基乙酸是通过苯甲酸酯与环己基溴镁反应并皂化产物制备的。二脂环和芳基脂环脂肪酸酸酐和酮。酸酐是通过将酸的碱金属盐与相应的酸卤化物反应制备的，而当通过将相应的α-羟基酸与五氯化磷反应制备的二脂环或芳基脂环-α-氯脂肪酸氯化物与锌处理时，形成酮。

  公开号：

  US02265184A1
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 溶剂黄146 、 铂 作用下， 生成 Drofenine
  参考文献：
  名称：

  Überdie Darstellung einiger承租人Ester替代Essigsäuren

  摘要：

  DOI：

  10.1002/hlca.19410240162

文献信息

• US2265185
  申请人：——

  公开号：——

  公开（公告）日：——
• CH220975
  申请人：——

  公开号：——

  公开（公告）日：——
• DE739151
  申请人：——

  公开号：——

  公开（公告）日：——
• CH223484
  申请人：——

  公开号：——

  公开（公告）日：——
• Basic esters and process of preparing same
  申请人：CIBA PHARM PROD INC

  公开号：US02265184A1

  公开（公告）日：1941-12-09

  532,943. Alkamine esters of disubstituted fatty acids. SOC. OF CHEMICAL INDUSTRY IN BASLE. Aug. 1, 1939, Nos. 22277 and 22278. Convention dates, Aug. 5, 1938 and June 20, 1939. [Class 2 (iii)] Di-alicyclic- or aryl-alicyclic-fatty acids are converted into their esters with amino-alcohols substituted in the amino group. Thus, the fatty acid or a reactive derivative thereof such as a halide, ester, anhydride or ketene, is reacted with the amino-alcohol ; or a reactive ester of the amino-alcohol is reacted with the fatty acid or salt thereof ; or the fatty acid or its reactive derivative may be combined with an alcohol containing a substituent, e.g. halogen, which is then replaced, on interaction with an amine by a substituted amino group. The products, which are useful therapeutically, may be converted into their quaternary salts. According to the examples, (1) dicyclohexylacetic acid 2-diethylamino-ethanol ester is prepared by reacting the acid chloride, prepared from the acid by means of thionyl chloride, with the amino-alcohol; its bromethylate is formed by heating with alkyl bromide and its bromomethylate, bromethylate and bromobenzylate are similarly prepared ; (2) phenyl-cyclohexylacetic acid is heated with chlorethyldiethylamine in the presence or absence of potassium carbonate to give the diethylamino-ethanol ester, which may be converted into its bromomethylate by treatment with methyl bromide ; the same esters of phenyl-cyclohexyl-propionic, phenyl - cyclohexyl - butyric, dicyclopentyl acetic, phenyl-cyclopentyl-acetic, phenyl-#<;SP>;1<;/SP>;- or #<;SP>;2<;/SP>;-cyclohexamyl-acetic and phenyl-#<;SP>;1<;/SP>;- or # <;SP>;2<;/SP>;-cyclopentenyl-acetic acids are similarly obtained ; also the piperidine-ethanol, diethylamino-n-butanol, diethylamino-ethanol, morpholino - ethanol, ethyl - acetoxyethylaminoethanol, ethyl-hydroxypropylamino-ethanol, methyl-propylamino-ethanol and m-dimethylaminocyclohexanol esters of phenyl-cyclohexylacetic acid. The following additional esters are referred to :-dicyclohexyl-acetic acid tropine ester, α:α<;SP>;1<;/SP>;-dicyclohexyl-α-hydroxyacetic acid diethylamino-ethanol ester, α-phenyl-α-cyclohexyl-α-hydroxyacetic acid diethylamino-ethanol ester, the phenyl-cyclohexyl-acetic acid esters of ecgonine methyl ester and phenyldimethylaminocyclohexyl-acetic acid diethylamino-ethanol ester. The Specification as open to inspection under Sect. 91 also describes the manufacture of alkamine esters of mono-alicyclic-fatty acids. Thus, cyclohexyl-acetic acid, prepared by reduction of phenylacetic acid with hydrogen in presence of platinum, is converted into its chloride by means of thionyl chloride and reacted with diethylamino-ethanol to give cyclohexylacetic acid diethylamino-ethanol ester. In analogous manner are prepared α-cyclohexylhydracrylic acid tropine and scopine esters (the acid is prepared by reduction of tropic acid with hydrogen in presence of platinum), α-cyclohexyl-α-propyl-acetic acid diethylaminoetbanol ester (the acid is obtained by hydrogenation of α-phenyl-α-propyl-acetic acid in presence of platinum), and cyclohexyl-diethylaminoethyl-acetic acid diethylamino-ethanol ester (the acid being prepared by reaction of phenylacetonitrile with diethylaminoethyl chloride in presence of sodamide, saponification of the nitrile and reduction of the product). Other acids that may be used are cyclohexenyl-fatty acids and hydronaphthalene-fatty acids. This subject-matter does not appear in the Specification as accepted. Di-alicyclic- and aryl-alicyclic-fatty acids. Phenyl-cyclohexyl-acetic acid is obtained by reaction of phenylacetonitrile with cyclohexyl bromide in presence of sodamide and saponification of the product. Similarly, by reaction of phenylacetonitrile with A , - or A 2-cyclohexenyl bromide, #<;SP>;1<;/SP>;- or # <;SP>;2<;/SP>;-cyclopentenyl bromide or dimethylaminocyclohexyl bromide, followed by saponification, the corresponding disubstituted acetic acids are obtained. Phenyl-cyclohexylpropionic and -butyric acids are prepared by reduction of an ester of diphenyl-propionic or - butyric acid with hydrogen in presence of a nickel catalyst, followed by saponification of the ester. Phenyl-cyclopentyl-acetic acid is obtained from a phenyl-cyclopentenyl-acetic acid by the action of mild reducing agents. α:α-Dicyclohexyl-α-hydroxyacetic acid results from the catalytic reduction of benzilic acid. α - Phenyl - x - cyclohexyl - α - hydroxyacetic acid is made by reacting a benzoyl-formic acid ester with cyclohexyl-magnesium bromide and saponifying the product. Di-alicyclic- and aryl-alicyclic-fatty acid anhydrides and -ketenes. The anhydrides are prepared by reacting an alkali metal salt of the acid with the corresponding acid halide, whilst the ketenes are formed when a di-alicyclic- or aryl-alicyclic-α-chlorofatty acid chloride, prepared by reacting the corresponding α-hydroxy acid with phosphorus pentachloride, is treated with zinc.

  532,943. 二取代脂肪酸的烷胺酯。巴塞尔化学工业协会。1939年8月1日，编号22277和22278。会议日期，1938年8月5日和1939年6月20日。[2（iii）类]二脂环或芳基脂环脂肪酸与氨基醇在氨基上取代的酯转化为它们的酯。因此，脂肪酸或其反应衍生物，如卤化物、酯、酸酐或酮，与氨基醇反应；或者氨基醇的反应酯与脂肪酸或其盐反应；或者脂肪酸或其反应衍生物可以与含有取代基（例如卤素）的醇结合，然后通过与胺作用替换为取代的氨基。这些在治疗上有用的产品可以转化为它们的季铵盐。根据示例，（1）二环己基乙酸2-二乙基氨基乙醇酯是通过将酸氯与氨基醇反应制备的，该酸氯是通过用亚砜氯制备的酸制备的；它的溴甲基酸酯通过与溴代烷反应形成，其溴甲基酸酯、溴乙酸酯和溴苄酸酯类似制备；（2）苯基环己基乙酸与氯乙基二乙胺在存在或不存在碳酸钾的情况下加热，得到二乙基氨基乙醇酯，可以通过与溴甲烷处理转化为其溴甲基酸酯；苯基环己基丙酸、苯基-环己基-丁酸、二环戊基乙酸、苯基-环戊基-乙酸、苯基-#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环己基-乙酸和苯基-#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环戊烯基-乙酸的相同酯也类似获得；还有苯基环己基乙酸的哌啶-乙醇、二乙基氨基正丁醇、二乙基氨基乙醇、吗啉-乙醇、乙基-乙酰氧乙基氨基乙醇、乙基-羟丙基氨基乙醇、甲基-丙基氨基乙醇和苯基环己基乙酸的m-二甲基氨基环己醇酯。还提到以下额外的酯：二环己基乙酸曲马多酯，α:α<;SP>;1<;/SP>;-二环己基-α-羟基乙酸二乙基氨基乙醇酯，α-苯基-α-环己基-α-羟基乙酸二乙基氨基乙醇酯，苯基-环己基乙酸酯的可卡因甲酯和苯基二甲基氨基环己基乙酸二乙基氨基乙醇酯。根据第91节开放检查的规范还描述了单脂环脂肪酸的烷胺酯的制备。因此，通过在铂存在下用氢还原苯乙酸制备环己基乙酸，将其氯化为环己基乙酸二乙基氨基乙醇酯。类似地，α-环己基羟基丙酸曲马多和斯科平酯（该酸通过在铂存在下用氢还原曲马酸制备）；α-环己基-α-丙基乙酸二乙基氨基乙醇酯（该酸通过在铂存在下用氢还原α-苯基-α-丙基乙酸制备），以及环己基-二乙基氨基乙基乙酸二乙基氨基乙醇酯（该酸通过苯乙腈与二乙基氨基乙基氯在苏打胺存在下反应，腈的皂化和产物的还原制备）。其他可能使用的酸是环己烯基脂肪酸和氢化萘脂肪酸。这个主题在接受的规范中没有出现。二脂环和芳基脂环脂肪酸。苯基环己基乙酸是通过苯乙腈与环己基溴在苏打胺存在下反应并皂化产物制备的。类似地，通过苯乙腈与A ，-或A 2-环己烯基溴、#<;SP>;1<;/SP>;-或#<;SP>;2<;/SP>;-环戊烯基溴或二甲基氨基环己基溴反应，然后皂化，得到相应的二取代乙酸。苯基环己基丙酸和-丁酸是通过在镍催化剂存在下用氢还原二苯基-丙酸或-丁酸酯，然后皂化酯制备的。苯基环戊基乙酸是通过温和还原剂作用于苯基环戊烯基乙酸制备的。α:α-二环己基-α-羟基乙酸是通过苯甲酸酮催化还原得到的。α-苯基-x-环己基-α-羟基乙酸是通过苯甲酸酯与环己基溴镁反应并皂化产物制备的。二脂环和芳基脂环脂肪酸酸酐和酮。酸酐是通过将酸的碱金属盐与相应的酸卤化物反应制备的，而当通过将相应的α-羟基酸与五氯化磷反应制备的二脂环或芳基脂环-α-氯脂肪酸氯化物与锌处理时，形成酮。