4-{(2S)-4-[(1R)-1-苯基乙基]吗啉-2-基}苯甲腈 | 1035374-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 4-{(2S)-4-[(1R)-1-苯基乙基]吗啉-2-基}苯甲腈
• 英文名称: 4-{(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl}benzonitrile
• 英文别名: 4-((2S)-4-((1R)-1-phenylethyl)morpholin-2-yl)benzonitrile；4-((S)-4-((R)-1-phenylethyl)morpholine-2-yl)benzonitrile；4-((S)-4-((R)-1-Phenylethyl)morpholin-2-yl)benzonitrile；4-[(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl]benzonitrile
• CAS: 1035374-46-9
• 化学式: C₁₉H₂₀N₂O
• 分子量: 292.381
• InChiKey: NJUJCVISMXJRKY-DNVCBOLYSA-N

物化性质

• 沸点：
  436.0±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-{(2S)-4-[(1R)-1-苯基乙基]吗啉-2-基}苯甲腈 、 羟胺 以 甲醇 、 环戊基甲醚 、 水 为溶剂， 反应 24.0h， 生成 N'-hydroxy-4-((S)-4-((R)-1-phenylethyl)morpholine-2-yl)benzamidine
  参考文献：
  名称：

  [EN] INTERMEDIATE COMPOUND FOR SYNTHESIZING PHARMACEUTICAL AGENT AND PRODUCTION METHOD THEREOF
  [FR] COMPOSÉ INTERMÉDIAIRE POUR SYNTHÉTISER UN AGENT PHARMACEUTIQUE ET SON PROCÉDÉ DE PRODUCTION

  摘要：

  公开号：

  WO2010104193A3
• 作为产物：
  描述：

  4-((2S)-4-((1R)-1-phenylethyl)morpholin-2-yl)benzaldehyde 在 盐酸羟胺 、 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 4-{(2S)-4-[(1R)-1-苯基乙基]吗啉-2-基}苯甲腈
  参考文献：
  名称：

  WO2008/78837

  摘要：

  公开号：

文献信息

• [EN] 6-PYRIMIDINYL-PYRIMID-2-ONE DERIVATIVE<br/>[FR] DÉRIVÉ DE 6-PYRIMIDINYLPYRIMID-2-ONE
  申请人：MITSUBISHI TANABE PHARMA CORP

  公开号：WO2009035162A1

  公开（公告）日：2009-03-19

  A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

  由化学式(I)代表的化合物或其药用盐：用于预防和/或治疗由tau蛋白激酶1异常活性引起的疾病，例如神经退行性疾病（如阿尔茨海默病）。
• Practical and Scalable Synthesis of a Benzonitrile Derivative via Palladium-Catalyzed Cyanation with Potassium Ferrocyanide
  作者：Masayuki Utsugi、Hiroki Ozawa、Eiji Toyofuku、Masanori Hatsuda

  DOI：10.1021/op400204g

  日期：2014.6.20

  reproducible synthetic method for the preparation of a benzonitrile derivative (1) from an aryl bromide (2) via Pd-catalyzed cyanation was established with dimethylacetamide (DMAc)–toluene as a mixed solvent. Optimization was examined by a design of experiments (DoE) technique to enhance reaction conversion and reduce the dimeric impurity 3, and desired benzonitrile derivative 1 was successfully obtained in high

  以二甲基乙酰胺（DMAc）-甲苯为混合溶剂，建立了一种实用且可重现的合成方法，该方法可通过钯催化的氰化反应从芳基溴化物（2）制备苄腈衍生物（1）。通过实验设计（DoE）技术对优化进行了检验，以提高反应转化率并减少二聚体杂质3，并成功地以117千克规模的优异质量控制以高收率成功获得了所需的苄腈衍生物1。
• 2-SUBSTITUTED-6-HETEROCYCLIC PYRIMIDONE DERIVATIVES AS TAU PROTEIN KINASE 1 INHIBITORS
  申请人：Watanabe Kazutoshi

  公开号：US20100113775A1

  公开（公告）日：2010-05-06

  A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein each R 1 represents hydrogen atom or the like; X represents oxygen atom or the like; A represents a C 3 -C 7 cycloalkyl group, a C 6 -C 10 aryl group or a heterocyclic group; R 6 represents a halogen atom or the like; s represents 0 or an integer of 1 to 5; Q represents a pyridine ring which may be substituted or pyrimidine ring; and R 2 represents hydrogen atom or the like, which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

  化合物的化学式为(I)，其光学活性异构体或药物可接受的盐：其中每个R1代表氢原子或类似物；X代表氧原子或类似物；A代表C3-C7环烷基，C6-C10芳基或杂环基；R6代表卤素原子或类似物；s代表0或1到5的整数；Q代表可能被取代的吡啶环或嘧啶环；R2代表氢原子或类似物，用于预防和/或治疗由tau蛋白激酶1的异常活性引起的疾病，如神经退行性疾病（例如阿尔茨海默病）。
• 6-PYRIMIDINYL-PYRIMID-4-ONE DERIVATIVE
  申请人：FUKUNAGA Kenji

  公开号：US20120252812A1

  公开（公告）日：2012-10-04

  A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

  化合物的化学式为(I)，或其药学上可接受的盐，用于预防和/或治疗由tau蛋白激酶1异常活性引起的疾病，例如神经退行性疾病（如阿尔茨海默病）。
• INTERMEDIATE COMPOUND FOR SYNTHESIZING PHARMACEUTICAL AGENT AND PRODUCTION METHOD THEREOF
  申请人：Furuya Rikizou

  公开号：US20120059165A1

  公开（公告）日：2012-03-08

  A production method of an optically active 2-4-(5-substituted-oxadiazolyl) phenyl}morpholine which is useful as an intermediate for synthesizing a pharmaceutical agent is provided and the method comprises the following steps 1) to 4): 1) reacting a bromophenylmorpholine with a hexacyanoferrate(II) or a hydrate thereof at a temperature of from 110° C. to 140° C. in a reaction mixture comprising a Na 2 CO 3 , an organophosphorus compound, and a palladium catalyst in a polar aprotic solvent alone or combination of a polar aprotic solvent and other polar aprotic solvent or hydrocarbon solvent to give a cyanophenylmorpholine; 2) reacting the cyanophenylmorpholine with hydroxylamine or hydroxylamine hydrochloride at a temperature of from 10° C. to 40° C. in an aprotic polar solvent to give a hydroxylamine derivative; 3) reacting the hydroxylamine derivative with an acylation reagent selected from the group consisting of aliphatic acyl halides, aromatic acyl halides, aliphatic acyl anhydrides and aromatic anhydrides; and 4) keeping the mixture obtained after step 3) at a temperature of from 60° C. to 140° C. to give a 2-4-(5-substituted-oxadiazolyl) phenyl}morpholine.

  提供了一种制备光学活性的2-4-(5-取代-噁唑基)苯基}吗啡啶的生产方法，该方法可用作合成药物的中间体，包括以下步骤1）至4）：1）在极性无水溶剂或极性无水溶剂和其他极性无水溶剂或碳氢溶剂的反应混合物中，以110℃至140℃的温度，使用Na2CO3、有机磷化合物和钯催化剂，将溴苯基吗啡与六氰合铁(II)或其水合物反应，得到氰苯基吗啡；2）在无水极性溶剂中，以10℃至40℃的温度，将氰苯基吗啡与羟胺或羟胺盐酸盐反应，得到羟胺衍生物；3）将羟胺衍生物与选自脂肪族酰卤、芳香族酰卤、脂肪族酰酐和芳香族酰酐的酰化试剂反应；4）将步骤3）得到的混合物保持在60℃至140℃的温度下，得到2-4-(5-取代-噁唑基)苯基}吗啡啶。