1,2-二氯-4-(异氰基甲基)苯 | 1197-36-0

• 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: 1,2-二氯-4-(异氰基甲基)苯
• 英文名称: 1,2-dichloro-4-(isocyanomethyl)benzene
• 英文别名: 3,4-Dichlorbenzylisonitril
• CAS: 1197-36-0
• 化学式: C₈H₅Cl₂N
• mdl: MFCD04117527
• 分子量: 186.04
• InChiKey: QMYVLWDYEJFVHW-UHFFFAOYSA-N

物化性质

• 沸点：
  129-130 °C(Press: 0.01 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  4.4
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  4,6-二氯-二甲硫基嘧啶 、 1,2-二氯-4-(异氰基甲基)苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 以50%的产率得到7-chloro-1-(3,4-dichlorophenyl)-5-(methylsulfanyl)imidazo[1,5-c]pyrimidine
  参考文献：
  名称：

  4,6-二氯嘧啶衍生物和苄基异氰化物一锅法合成咪唑并[1,5-c]嘧啶衍生物

  摘要：

  A convenient method for the synthesis of imidazo[1,5-c]pyrimidine derivatives has been developed. Thus, benzyl isocyanides are treated with sodium hydride in DMF at 0 degrees C to generate the corresponding benzyl anions, which are allowed to react with 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) to afford 1-aryl-7-chloro-5-(methylsulfanypimidazo[1,5-c]pyrimidines in one pot in moderate yields.

  DOI：

  10.3987/com-16-13616
• 作为产物：
  描述：

  N-(3,4-二氯苄基)甲酰胺 在 methoxycarbonylsulfamoyl-triethylammmonium hydroxide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 1,2-二氯-4-(异氰基甲基)苯
  参考文献：
  名称：

  NEW COMPOUNDS I/418

  摘要：

  提供了式I的化合物， 其中R1至R7在描述中给出了它们的含义，这些化合物在预防和治疗心律失常方面非常有用，特别是房性和室性心律失常。

  公开号：

  US20080015237A1

文献信息

• [EN] ISOINDOLINE DERIVATIVES COMPRISING AN ADDITIONAL HETEROCYCLIC GROUP AND THEIR USE IN THE TREATMENT OF PAIN DISORDERS<br/>[FR] DÉRIVÉS ISOINDOLINE COMPRENANT UN GROUPE HÉTÉROCYCLIQUE SUPPLÉMENTAIRE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DE LA DOULEUR
  申请人：ASTRAZENECA AB

  公开号：WO2009145718A1

  公开（公告）日：2009-12-03

  Compounds of formula I are claimed, wherein R1is hydrogen, C1_3alkyl, C1_3alkoxy, cyano, hydroxy or halo; wherein C1-3alkyl may optionally be substituted by one or more substituents independently selected from hydroxy, C1-3alkoxy orfluoro; and wherein Ci^alkoxy may optionally be substituted by one or more fluoro; m is 1 or 2; R2 and R3 is each and independently selected from hydrogen, Ci_4haloalkyl, C1_4haloalkoxy, halo, C1_4alkoxy, C1_4alkyl and C3_7cycloalkyloxy; and wherein said C3_7cycloalkyloxy may optionally be substituted by one or more fluoro; and whereas both R2 and R3 can not be hydrogen; Het is selected from any one of pyridinyl, pyrazinyl, isoxazolyl, pyrazolyl, indolyl, triazolyl and pyrimidinyl, wherein each such heteroaryl may optionally be substituted by one or more X4; X4 is halo, C1-3alkyl, C1-3alkyl0C1-3alkyl, -CH(CH3)-O-C(CH3)3,C1_4alkoxy, cyano, or hydroxyl, or Ci_2hydroxyalkyl;; and wherein said C1-3alkyl, C 1-3alkylOC1-3alkyl, -CH(CH3)-O-C(CH3)3, or C1_4alkoxy may each optionally be substituted by one or more fluoro; L1 is C1_4alkylene, which may optionally be fluorinated or hydroxylated; and L2 is C1-3alkylene; with the exception of the compounds: 2-[1-(1,5-dimethyl-lH-pyrazol-4-yl)ethyl]-5,7-dimethoxy-3-oxo-N-[2-(trifluoromethyl)benzyl]isoindoline-1-carboxamide; N-(4-fluorobenzyl)-3-oxo-2-(-pyridin-4-yletyl)isoindoline-1-carboxamide and N-(2-chlorobenzyl)-2[2-(1H-indol-3-yl)-1-methyletyl]-3-oxoisoindoline-1-carboxamide; The invention further relates to pharmaceutical compositions containing said compounds and to the use of said compounds in therapy.

  公式I的化合物被要求，其中R1是氢，C1-3烷基，C1-3烷氧基，氰基，羟基或卤素；其中C1-3烷基可以选择性地被一个或多个取代基取代，这些取代基独立地选自羟基，C1-3烷氧基或氟基；而C1-3烷氧基可以选择性地被一个或多个氟基取代；m为1或2；R2和R3分别且独立地选自氢，C1-4卤代烷基，C1-4卤代烷氧基，卤素，C1-4烷氧基，C1-4烷基和C3-7环烷氧基；其中所述的C3-7环烷氧基可以选择性地被一个或多个氟基取代；而且R2和R3都不能是氢；Het选自吡啶基，吡嗪基，异噁唑基，吡唑基，吲哚基，三唑基和嘧啶基中的任何一种，其中每种这样的杂环烷基可以选择性地被一个或多个X4取代；X4是卤素，C1-3烷基，C1-3烷氧基C1-3烷基，-CH(CH3)-O-C(CH3)3，C1-4烷氧基，氰基，或羟基，或C1-2羟基烷基；而所述的C1-3烷基，C1-3烷氧基C1-3烷基，-CH(CH3)-O-C(CH3)3，或C1-4烷氧基可以选择性地被一个或多个氟基取代；L1是C1-4烷基，可以选择性地被氟化或羟基化；而L2是C1-3烷基；除了以下化合物：2-[1-(1,5-二甲基-1H-吡唑-4-基)乙基]-5,7-二甲氧基-3-氧代-N-[2-(三氟甲基)苯甲基]异吲哚啉-1-羧酰胺；N-(4-氟苯甲基)-3-氧代-2-(-吡啶-4-基乙基)异吲哚啉-1-羧酰胺和N-(2-氯苯甲基)-2[2-(1H-吲哚-3-基)-1-甲基乙基]-3-氧代异吲哚啉-1-羧酰胺；本发明还涉及含有所述化合物的药物组合物以及所述化合物在治疗中的使用。
• [EN] 2, 3, 4, 5-TETRAHYDROBENZO[F][1, 4]OXAZEPINE-5-CARBOXYLIC ACID AMIDE DERIVATIVES AS GAMMA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DERIVES D'AMIDE D'ACIDE 2, 3, 4, 5-TETRAHDROBENZO`F! `1, 4!OXAZEPINE-5-CARBOXYLIQUE TENANT LIEU D'INHIBITEURS DE LA GAMMA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004100958A1

  公开（公告）日：2004-11-25

  The invention relates to benzoxazepinone derivatives of formula (I) wherein R1 is hydrogen, lower alkoxy, halogen or -NR'R'; n is 1 or 2; R',R' are independently from each other hydrogen or lower alkyl; R2 is hydrogen, lower alkyl, -(CH2)m-cycloalkyl, -(CH2)m-phenyl or -(CH2)m-O-lower alkyl; m is 0,1or 2; R3 is lower alkyl, -(CH2)m-C(O)O-lower alkyl, cycloalkyl or -(CH2)m-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen or lower alkyl; R4 is -(CH2)ο-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen, trifluoromethyl, -NR'R', nitro or _SO2NH2, or is - cycloalkyl, unsubstituted or substituted by phenyl, or is - (CR'R')ο-heterocyclyl, selected from the group defined in claim 1 and o is 1 or 2; and to pharmaceutically suitable acid addition salts thereof. These compounds are good Ϝ-secretase inhibitors for the treatment of Alzheimer's disease.

  本发明涉及公式（I）的苯并噁唑啉酮衍生物，其中R1为氢、低碳氧基、卤素或-NR'R'；n为1或2；R'，R'各自独立地为氢或低碳基；R2为氢、低碳基、-(CH2)m-环烷基、-(CH2)m-苯基或-(CH2)m-O-低碳基；m为0、1或2；R3为低碳基、-(CH2)m-C（O）O-低碳基、环烷基或-(CH2)m-苯基，未经置换或经过一或两个置换基从卤素或低碳基的群中选择；R4为-(CH2)ο-苯基，未经置换或经过一或两个置换基从卤素、三氟甲基、-NR'R'、硝基或_SO2NH2的群中选择，或为-环烷基，未经置换或经过苯基置换，或为-(CR'R')ο-杂环基，从权利要求1中定义的群中选择，o为1或2；以及其药学上适宜的酸盐。这些化合物是治疗阿尔茨海默病的良好Ϝ-分泌酶抑制剂。
• Benzoxazepinone derivatives
  申请人：——

  公开号：US20040235819A1

  公开（公告）日：2004-11-25

  The invention relates to benzoxazepinone derivatives of formula 1 wherein R 1 , R 2 , R 3 , R 4 , and n are as defined in the specification and to a pharmaceutically suitable acid addition salt thereof. These compounds are good &ggr;-secretase inhibitors for the treatment of Alzheimer's disease.

  该发明涉及公式1中的苯并噁唑酮衍生物，其中R1，R2，R3，R4和n如规范中所定义，并且其药物适宜的酸盐。这些化合物是治疗阿尔茨海默病的良好&ggr;-分泌酶抑制剂。
• 1,4-Thienodiazepine-2,5-diones via MCR (I): Synthesis, Virtual Space and p53-Mdm2 Activity
  作者：Yijun Huang、Siglinde Wolf、Michal Bista、Lidio Meireles、Carlos Camacho、Tad A. Holak、Alexander Dömling

  DOI：10.1111/j.1747-0285.2010.00989.x

  日期：——

  1,4‐Thienodiazepine‐2,5‐diones have been synthesized via the Ugi‐Deprotection‐Cyclization (UDC) approach starting from Gewald 2‐aminothiophenes in a convergent and versatile manner. The resulting scaffold is unprecedented, cyclic, and peptidomimetic with four points of diversity introduced from readily available starting materials. In addition to eighteen synthesized and characterized compounds, a virtual compound library was generated and evaluated for chemical space distribution and drug‐like properties. A small focused compound library of 1,4‐thienodiazepine‐2,5‐diones has been screened for the activity against p53‐Mdm2 interaction. Biological evaluations demonstrated that some compounds exhibited promising antagonistic activity.
• Discovery of protein–protein binding disruptors using multi-component condensations small molecules
  作者：Karim Bedjeguelal、Hugues Bienaymé、Antoine Dumoulin、Stéphane Poigny、Philippe Schmitt、Eric Tam

  DOI：10.1016/j.bmcl.2006.05.014

  日期：2006.8

  A series of small molecule compounds interfering with the binding process of VEGF and NRP1 has been identified and further optimized. Full synthetic details as well as SAR are reported which demonstrate that expeditious MCC-based syntheses may lead to valuable molecules addressing challenging targets such as protein-protein interactions. Preliminary functional assay data confirm that these compounds may be further developed toward drug candidates. (c) 2006 Elsevier Ltd. All rights reserved.