1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 51054-41-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,7-dimethoxy-1-cyanomethylene-1,2,3,4-tetrahydroisoquinoline；(2Z)-2-(6,7-dimethoxy-3,4-dihydro-2H-isoquinolin-1-ylidene)acetonitrile
• CAS: 51054-41-2
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: KHZAKBHKVKPSDN-JYOAFUTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 sodium hydroxide 、 PPA 作用下， 生成 1-carbamidomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Pyrimido (6,1-a)isoquinolin-4-one derivatives

  摘要：

  披露的是嘧啶并[6,1-a]异喹啉-4-酮化合物，可用作降压剂、支气管扩张剂和抗过敏药物，以及其制备中有用的中间体，以及制备这些化合物和中间体的方法。

  公开号：

  US04482556A1
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 27.17h， 生成 1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  10.1002/bkcs.12846

  摘要：

  AbstractWhile a pharmaceutically intriguing scaffold, 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ), has precedently been prepared from diverse tetrahydroisoquinolines (THIQs) using elaborate conditions, convenient metal‐free methods were discovered from condensation of cyanomethylene‐THIQ (1) and α‐halo‐ketones or aldehydes (1a) to afford 15 DHPIQs (2–16) in moderate yields by employing unique reactivities of the secondary amine and α‐carbon to the nitrile of 1. Preliminary biological studies with chronic myelogenous leukemia K562 and adriamycin‐resistant K562 (K562/ADM) cells exhibited some of the DHPIQs tested were active in the both cell lines. In particular, cyclohexyl‐fused DHPIQ (10) showed GI50 values of 9.79 and 13.60 μM in K562 and K562/ADM cells, respectively. Based on the flow cytometry analysis of 10, the anti‐cancer activity could be from apoptosis‐related mechanisms. Overall, this DHPIQ scaffold may be further optimized to discover clinically meaningful anti‐leukemic agents overcoming adriamycin resistance.

  DOI：

  10.1002/bkcs.12846

文献信息

• Cerium(III)-Catalyzed Cyclizations with 1-Cyanomethylene Tetrahydroisoquinoline: Substituent Controlled Formation of Fused Pyrroles or Pyridines
  作者：Péter Nemes、Zoltán Vincze、Barbara Balázs、Gábor Tóth、Pál Scheiber

  DOI：10.1055/s-2004-822904

  日期：——

  1-Cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline reacts with α,β-unsaturated aldehydes and ketones in presence of cerium(III) chloride, to yield benzo[a]quinolizines. α-Alkyl substituted unsaturated aldehydes under the same conditions, however, afford pyrrolo[2,1-a]isoquinolines.

  1-氰基亚甲基-6,7-二甲氧基-1,2,3,4-四氢-异喹啉在氯化铈 (III) 存在下与 α,β-不饱和醛和酮反应，生成苯并[a] 喹啉。然而，α-烷基取代的不饱和醛在相同条件下得到吡咯并[2,1-a]异喹啉。
• [EN] PYRROLODIHYDROISOQUINOLINES AS PDE10 INHIBITORS<br/>[FR] PYRROLODIHYDROISOQUINOLINES COMME INHIBITEURS DE PDE10
  申请人：ALTANA PHARMA AG

  公开号：WO2005003129A1

  公开（公告）日：2005-01-13

  The invention relates to novel pyrrolodihydroisoquinoline derivatives, which are efficacious inhibitors of PDE10.

  这项发明涉及新颖的吡咯二氢异喹啉衍生物，它们是有效的PDE10抑制剂。
• [3+3] Cyclization reactions of β-nitroenamines and β-enaminonitriles with α,β-unsaturated carboxylic acid chlorides
  作者：Mihály V. Pilipecz、Tamás R. Varga、Zoltán Mucsi、Pál Scheiber、Péter Nemes

  DOI：10.1016/j.tet.2008.03.090

  日期：2008.6

  New indolizidines, quinolizidines, and octahydro-pyrido[1,2-a]azepines of lactam type were synthesized from 2-nitromethylene-pyrrolidine, -piperidine, and -hexahydroazepine, respectively, by [3+3] cyclizations with α,β-unsaturated carboxylic acid chlorides. In the case of quinolizidines, a double bond migration was observed, and explained in terms of amidity percentage. Cyanomethylene-pyrrolidine gave

  通过[3 + 3]与α，β-的环化反应，分别由2-硝基亚甲基-吡咯烷，-哌啶和-六氢a庚啶合成了内酰胺型的新吲哚并咪唑，喹唑烷和八氢吡啶并[1,2- a ]氮杂ze。不饱和羧酸氯化物。在喹喔啉类的情况下，观察到双键迁移，并且用酰胺百分比来解释。当分别使用简单的开链酰基氯或肉桂酰氯时，氰基亚甲基-吡咯烷产生内酰胺类型的吲哚并咪唑，而1-氰基亚甲基-四氢异喹啉的转化产生内酰胺和酮。
• Novel Microwave-assisted [3+3] Cyclocondensations with 1-Cyanomethylene Tetrahydroisoquinoline
  作者：Péter Nemes、Zoltán Vincze、Barbara Balázs、Gábor Tóth、Pál Scheiber

  DOI：10.1055/s-2003-36796

  日期：——

  α,β-Unsaturated aldehydes and ketones react with 1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline in microwave-enhanced reactions affording regioselectively 6,7-dihydro-4H-benzo[a]quinolizines and 6,7-dihydro-2H-benzo[a]quinolizines, respectively.

  α,β-不饱和醛和酮在微波增强反应中与 1-氰基亚甲基-6,7-二甲氧基-1,2,3,4-四氢异喹啉反应，区域选择性地生成 6,7-二氢-4H-苯并[a]喹嗪分别是6,7-二氢-2H-苯并[a]喹嗪。
• Pharmaceutically effective novel 3,4-dihydro-1,2- and 1,3-thiozolo [4,3a] i
  申请人：Chinoin Pharmaceutical and Chemical Works Ltd.

  公开号：US03979397A1

  公开（公告）日：1976-09-07

  The invention relates to new thiazoloisoquinolines of the general formula (I), or salts thereof, ##SPC1## Wherein A stands for a group of the formula ##EQU1## R.sup.1 stands for hydrogen, hydroxy, alkoxy or aralkoxy, R.sup.2 stands for hydrogen, hydroxy, alkoxy or aralkoxy, R.sup.3 stands for hydrogen, alkyl, aryl, nitro, carboxy or a carboxy derivative, and Y stands for oxygen, sulfur, or a group of the formula =N--R.sup.4, wherein R.sup.4 stands for hydrogen, alkyl, aryl, acyl, alkylsulfonyl or arylsulfonyl. These new compounds can be used in practice as heart medicines or respiratory analeptics. The new compounds according to the invention can be prepared as follows: an isoquinoline of the general formula (II) or a salt thereof ##SPC2## Wherein R.sup.5 stands for hydrogen, hydroxy, alkoxy or aralkoxy, R.sup.6 stands for hydrogen, hydroxy, alkoxy or aralkoxy, R.sup.7 stands for hydrogen, alkyl, aryl, carboxy or a carboxy derivative, and X stands for hydrogen, halogen or mercapto, Is reacted with a reactive carbonic acid derivative, provided that at least one of the reactants contains a sulfur atom, and/or an isoquinoline of the general formula (III) ##SPC3## wherein R.sup.5, R.sup.6 and R.sup.7 each have the same meanings as defined above, and Y' stands for oxygen, sulfur or a group of the formula =N--R.sup. 8, wherein R.sup.8 represents hydrogen, alkyl, aryl, acyl, arylsulfonyl or alkylsulfonyl, is oxidized, and/or substituents A', R.sup.5, R.sup.6 and R.sup.7 of the obtained thiazoloisoquinoline of the general formula (IA) ##SPC4## wherein A' stands for a group of the formula ##EQU2## and R.sup.5, R.sup.6, R.sup.7 and Y' each have the same meanings as defined above, are converted into those required in the end-products.

  本发明涉及一般式(I)的新噻唑异喹啉或其盐，其中A代表式的基团；R1代表氢、羟基、烷氧基或芳基氧基；R2代表氢、羟基、烷氧基或芳基氧基；R3代表氢、烷基、芳基、硝基、羧基或羧基衍生物；Y代表氧、硫或式的基团，其中R4代表氢、烷基、芳基、酰基、烷基磺酰基或芳基磺酰基。这些新化合物可实际用作心脏药物或呼吸兴奋剂。根据本发明，可以如下制备新化合物：一般式(II)的异喹啉或其盐或一般式(III)的异喹啉，其中R5、R6和R7具有上述定义的相同含义，Y'代表氧、硫或式的基团，其中R8代表氢、烷基、芳基、酰基、芳基磺酰基或烷基磺酰基，进行反应，提供至少一个反应物含有硫原子的反应性碳酸衍生物，和/或氧化一般式(III)，并/或将所得到的一般式(IA)的噻唑异喹啉的取代基A'、R5、R6和R7转化为所需的最终产物。