2-[3-(2-氰基丙烷-2-基)-5-(1,5-二氢-1,2,4-三唑-4-基甲基)苯基]-2-甲基丙腈 | 120511-92-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[3-(2-氰基丙烷-2-基)-5-(1,5-二氢-1,2,4-三唑-4-基甲基)苯基]-2-甲基丙腈
• 中文别名: 2-[3-(1-氰基-1-甲基-乙基)
• 英文名称: α,α,α',α'-tetramethyl-5-(4H-1,2,4-triazol-4ylmethyl)-1,3-benzene-diacetonitrile
• 英文别名: 2,2'-(5-((1 H-1,3,5-triazol-1-yl)methyl)-1,3-phenylene)bis(2-methylpropanenitrile)；2,2'-[5-(4H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]-di(2-methyl-propionitrile)；2,2'-[5-(4H-1,2,4-triazol-4-ylmethyl)-1,3-phenylene]di(2-methylpropiononitrile)；isoanastrozole；2,2'-[5-(4H-1,2,4-triazol-4-ylmethyl)-1,3-phenylene]bis(2-methylpropanenitrile)；2-[3-(2-cyanopropan-2-yl)-5-(1,2,4-triazol-4-ylmethyl)phenyl]-2-methylpropanenitrile
• CAS: 120511-92-4
• 化学式: C₁₇H₁₉N₅
• mdl: MFCD19105534
• 分子量: 293.371
• InChiKey: UHMBCUNKPNNBSD-UHFFFAOYSA-N

物化性质

• 沸点：
  469.7±55.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  78.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  应存放在室温、干燥且密封的环境中。

反应信息

• 作为产物：
  描述：

  1H-1,2,4-三唑 、 5-溴甲基-a,a,a',a'-四甲基-1,3-二乙氰基苯 在 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 4.5h， 生成 2-[3-(2-氰基丙烷-2-基)-5-(1,5-二氢-1,2,4-三唑-4-基甲基)苯基]-2-甲基丙腈 、 阿那曲唑
  参考文献：
  名称：

  A process for preparing trisubstituted phenyl derivatives comprising a (1H-1,2,4-triazol-1-yl)alkyl group

  摘要：

  本发明一般涉及有机化学领域，特别涉及制备包含（1H-1,2,4-三唑-1-基）烷基基团的苯基衍生物，例如阿那替珠（2,2'-(5-((1H-1,2,4-三唑-1-基)甲基)-1,3-苯基)双(2-甲基丙腈)）。

  公开号：

  EP2343278A1

文献信息

• Process for the preparation of anastrozole and intermediates thereof
  申请人：Khile Shahaji Anil

  公开号：US20060189670A1

  公开（公告）日：2006-08-24

  A process for the preparation of anastrozole is provided, the process comprising: (a) reacting 3,5-bis(1-cyano-1-methylethyl)benzyl halide with a 4-Z-1,2,4-triazole compound of the formula wherein Z is a protecting group to produce 2,2′-[5-(4-Z-1,2,4-triazolium-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile) halide; and (b) deprotecting the 2,2′-[5-(4-Z-1,2,4-triazolium-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile)halide to produce anastrozole. Also provided is anastrozole substantially free of its isomers.

  提供一种制备阿那曲唑的方法，该方法包括：(a)将3,5-双(1-氰基-1-甲基乙基)苄卤化物与具有以下结构的4-Z-1,2,4-三唑化合物发生反应，其中Z是保护基，以产生2,2′-[5-(4-Z-1,2,4-三唑-1-基甲基)-1,3-苯基]二(2-甲基丙腈)卤化物；和(b)去保护2,2′-[5-(4-Z-1,2,4-三唑-1-基甲基)-1,3-苯基]二(2-甲基丙腈)卤化物以产生阿那曲唑。还提供了基本不含异构体的阿那曲唑。
• Process for the Preparation of 2,2'-[5-(1H-1,2,4-Triazole-1-Ylmethyl) -1,3-Phenylene] Di (2-Methylpropionitrile)
  申请人：Radhakrishnan Tarur Venkatasubramanian

  公开号：US20080207915A1

  公开（公告）日：2008-08-28

  The present invention discloses a process for the preparation of Anastrozole of the formula I in high purity and in high yield. 3,5-bis(halomethyl)toluene is prepared by reacting mesitylene with N-halosuccinimide in the presence of light or dibenzoyl peroxide or azobis isobutyronitrile as a catalyst and in a chlorinated solvent. 3,5-bis(halomethyl)toluene is cyanated with metal cyanide in the presence of a catalyst and in water, organic solvent or mixture thereof at temperature of 40 to 60° C. to obtain 2,2′-(5-methyl-1,3 phenylene)diacetonitrile which is further methylated with iodomethane in the presence of base and an organic solvent at temperature of 0 to 15° C. to obtain 2,2′-(5-methyl-1,3-phenylene)di(2-methyl-propiononitrile). The product obtained is treated with N-halosuccinimide in the presence of a catalyst and in a chlorinated solvent at temperature of 60 to 100° C. to obtain 2,2′-(5-halomethyl-1,3-phenylene)di(2-methyl propionitrile) which was further treated with potassium or sodium salt 1,2,4-triazole at temperature of 20 to 50° C. in dimethyl formamide to obtain crude 2,2′-[5-( 1 H-1,2,4-triazole-1-ylmethyl)-1,3-phenylene]di(2-methyl-propionitrile). The crude product is purified by column chromatography using a stationary phase and a mobile phase followed by recrystallization with a solvent or mixture of solvents to obtain highly pure Anastrozole.

  本发明揭示了一种制备高纯度和高产率的化学式I的阿那曲唑的方法。首先，通过将间二甲苯与N-卤代琥珀酰亚胺在光照或二苯甲酰过氧化物或异丁腈偶氮叔丁酰胺存在下在氯化溶剂中反应制备3,5-双(卤甲基)甲苯。然后，在催化剂的存在下，将3,5-双(卤甲基)甲苯与金属氰化物在水、有机溶剂或二者混合物中在40至60°C的温度下反应，得到2,2′-(5-甲基-1,3-苯基)双乙腈。接着，在碱和有机溶剂存在下，在0至15°C的温度下，将2,2′-(5-甲基-1,3-苯基)双乙腈与碘甲烷反应甲基化，得到2,2′-(5-甲基-1,3-苯基)双(2-甲基-丙酰亚胺)。随后，将所得产物在催化剂的存在下，在60至100°C的温度下，与N-卤代琥珀酰亚胺在氯化溶剂中反应，得到2,2′-(5-卤甲基-1,3-苯基)双(2-甲基丙腈)。最后，将该产物与钾盐或钠盐1,2,4-三唑在20至50°C的温度下在二甲基甲酰胺中反应，得到粗的2,2′-[5-(1H-1,2,4-三唑-1-基甲基)-1,3-苯基]双(2-甲基丙腈)。通过柱层析和再结晶，使用固定相和流动相纯化粗产品，最终获得高纯度的阿那曲唑。
• PROCESS FOR MAKING ANASTROZOLE
  申请人：Benes Michal

  公开号：US20080076933A1

  公开（公告）日：2008-03-27

  A process for making anastrozole using a 1-substituted triazole can reduce formation of the undesired iso-anastrozole. A typical process is represented by wherein compound (10) is a 1-substituted triazole and compound (1) is anastrozole.

  使用1-取代三唑制备阿那曲唑的过程可以减少不期望的异构体异构阿那曲唑的形成。典型的过程如下所示，其中化合物（10）是1-取代三唑，化合物（1）是阿那曲唑。
• (Substituted aralkyl) heterocyclic compounds
  申请人：Imperial Chemical Industries plc

  公开号：US04935437A1

  公开（公告）日：1990-06-19

  A (substituted-aralkyl)heterocyclic compound of the formula I ##STR1## wherein R.sup.1 is an azido, carbamoyl, cyano, formyl, hydroxy or nitro radical, a 1-6C 1-hydroxyalkyl, alkoxy, alkylcarbamoyl, alkylthio, alkylsulphinyl or alkylsulphonyl radical, a 2-cyanoethyl radical, optionally bearing one to four 1-6C alkyl substituents, or a 2-6C alkanoyl, halogenoalkanoyl, alkanoyloxy, alkanoylamino, dialkylcarbamoyl or alkoxycarbonyl radical; R.sup.2 and R.sup.3, which may be the same or different, are each a hydrogen atom, a 1-6C alkyl, dueterioalkyl or halogenoalkyl radical, or a phenyl or phenyl(1-6C alkyl) radical, in each of which the phenyl may optionally bear one or more substituents; or R.sup.2 and R.sup.3, together with the carbon atom to which they are attached, may form a 3- to 6-membered ring; or R.sup.1 R.sup.2 R.sup.3 C- is a 1,1-dicyanoethyl or trifluoromethylsulphonyl radical; R.sup.4 is a hydrogen or halogen atom, a cyano or nitro radical or a 1-6C alkyl or halogenoalkyl radical; R.sup.5 has any of the values defined above for the group R.sup.1 R.sup.2 R.sup.3 C but is not necessarily the same as R.sup.1 R.sup.2 R.sup.3 C, or has any of the values defined above for R.sup.4 but is not necesarily the same as R.sup.4, or is a carbamoyl, 1-pyrrolidinyl-carbonyl, piperidinocarbonyl, morpholinocarbonyl or nitro radical, a 1-6C alkoxy or halogenoalkoxy radical or a 2-6C alkanoyl or alkoxy-carbonyl radical; A is a methylene or ethylene radical optionally bearing one or more substituents selected from deuterium and halogen atoms, carbamoyl, cyano and hydroxy radicals, 1-6C alkyl and alkoxy radicals, and 2-6C alkanoyloxy radicals provided that when A is linked to R.sup.6 through a nitrogen atom thereof, it may not bear a hydroxy, alkoxy or alkanoyloxy substituent on the carbon atom adjacent to such nitrogen atoms; and R.sup.6 is a 1H-1,2,4-triazol-1-yl, 4H-1,2,4-triazol-4-yl, 1H-imidazol-1-yl, 5-cyano-1H-imidazol-1-yl, 3-pyridyl or 5-pyrimidinyl radical, or a 1H-imidazol-1-yl radical, bearing at the 5-position thereof a 1-6C alkyl substituent which is itself optionally substituted by one or more carbamoyl, cyano, hydroxy or 2-6C alkoxycarbonyl radicals; and provided that when R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are hydrogen, A is a methylene radical and R.sup.6 is a 3-pyridyl radical, R.sup.1 is not a cyano, hydroxy or hydroxymethyl radical, and when R.sup.1 is a hydroxy radical, R.sup.3, R.sup.4 and R.sup.5 are hydrogen, A is a methylene radical and R.sup.6 is 3-pyridyl, R.sup.2 is not a methyl or a 2-chloro-1-methylethyl radical, and provided that when R.sup.1 is a methoxycarbonyl radical, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are hydrogen and A is a methylene radical, R.sub.1 is not a 1H-imidazol-1-yl radical; and the pharmaceutically acceptable acid addition salts thereof.

  一种公式I的（替代芳基）杂环化合物 其中R.sup.1是azido、carbamoyl、cyano、formyl、羟基或硝基基团，1-6C 1-羟基烷基、烷氧基、烷基氨甲酰、烷基硫醚、烷基磺醚或烷基磺酰基团，2-氰乙基基团，可选地带有一到四个1-6C烷基取代基，或2-氰乙基基团，可选地带有一到四个1-6C烷基取代基，或2-6C烷酰基、卤代烷酰基、烷酰氧基、烷酰胺基、二烷基氨基甲酰基或烷氧羰基基团；R.sup.2和R.sup.3，可能相同也可能不同，分别是氢原子、1-6C烷基、二氘烷基或卤代烷基基团，或苯基或苯基（1-6C烷基）基团，其中苯基可能可选地带有一个或多个取代基；或R.sup.2和R.sup.3，连同它们附着的碳原子，可形成3-至6-成员环；或R.sup.1 R.sup.2 R.sup.3 C-是1,1-双氰乙基或三氟甲基磺酰基团；R.sup.4是氢或卤原子、氰基或硝基基团或1-6C烷基或卤代烷基基团；R.sup.5具有上述R.sup.1 R.sup.2 R.sup.3 C基团定义的任何值，但不一定与R.sup.1 R.sup.2 R.sup.3 C相同，或具有上述R.sup.4定义的任何值，但不一定与R.sup.4相同，或是carbamoyl、1-吡咯烷基羰基、哌啶基羰基、吗啉基羰基或硝基基团，1-6C烷氧基或卤代烷氧基基团或2-6C烷酰基或烷氧羰基团；A是一个亚甲基或乙烯基基团，可选地带有一个或多个取代基，所述取代基选自氘和卤原子、carbamoyl、氰基和羟基基团、1-6C烷基和烷氧基团，以及2-6C烷酰氧基基团，条件是当A通过其氮原子连接到R.sup.6时，不能在相邻于该氮原子的碳原子上带有羟基、烷氧基或烷酰氧基取代基；R.sup.6是1H-1,2,4-三唑-1-基、4H-1,2,4-三唑-4-基、1H-咪唑-1-基、5-氰基-1H-咪唑-1-基、3-吡啶基或5-嘧啶基基团，或1H-咪唑-1-基，其在其5-位置带有一个1-6C烷基取代基，该取代基本身可选地被一个或多个carbamoyl、氰基、羟基或2-6C烷氧羰基团取代；条件是当R.sup.2、R.sup.3、R.sup.4和R.sup.5为氢时，A是亚甲基基团，R.sup.6是3-吡啶基团，R.sup.1不是氰基、羟基或羟甲基基团，当R.sup.1为羟基基团时，R.sup.3、R.sup.4和R.sup.5为氢，A是亚甲基基团，R.sup.6是3-吡啶基团，R.sup.2不是甲基或2-氯-1-甲基乙基基团，条件是当R.sup.1为甲氧羰基基团时，R.sup.2、R.sup.3、R.sup.4和R.sup.5为氢，A是亚甲基基团，R.sub.1不是1H-咪唑-1-基；以及其药用可接受的酸盐。
• [EN] A PROCESS FOR PREPARING TRISUBSTITUTED PHENYL DERIVATIVES COMPRISING A (1H-1,2,4-TRIAZOL-1-YL)ALKYL GROUP<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS PHÉNYLE TRISUBSTITUÉS COMPRENANT UN GROUPE (1H-1,2,4-TRIAZOL-1-YLE) ALKYLE
  申请人：HEXAL AG

  公开号：WO2011083079A1

  公开（公告）日：2011-07-14

  The present invention relates in general to the field of organic chemistry, and in particular to the preparation of phenyl derivatives comprising a (1H-1,2,4-triazol-1-yl)alkyl group such as anastrozole (2,2'-(5-((1H-1,2,4-triazol-1-yl)methyl)-1,3-phenylene) bis(2-methyl-propanenitrile).

  本发明一般涉及有机化学领域，特别涉及制备含有(1H-1,2,4-三唑-1-基)烷基基团的苯基衍生物，例如阿那曲唑（2,2'-(5-((1H-1,2,4-三唑-1-基)甲基)-1,3-苯基)双(2-甲基丙腈)）。