4-cyano-3-amino-1-(N-tert-butoxycarbonyl)-3,4-pyrroline | 1227461-24-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 4-cyano-3-amino-1-(N-tert-butoxycarbonyl)-3,4-pyrroline
• 英文别名: tert-butyl 3-amino-4-cyano-2,5-dihydro-1H-pyrrole-1-carboxylate；tert-butyl 3-amino-4-cyano-2,5-dihydropyrrole-1-carboxylate
• CAS: 1227461-24-6
• 化学式: C₁₀H₁₅N₃O₂
• mdl: MFCD21602487
• 分子量: 209.248
• InChiKey: ZUWAEUIARMWGSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P305+P351+P338,P332+P313,P337+P313,P362
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  4-cyano-3-amino-1-(N-tert-butoxycarbonyl)-3,4-pyrroline 在 亚硝酸特丁酯 、 copper(ll) bromide 作用下， 以 乙腈 、 正丁醇 为溶剂， 反应 112.0h， 生成 tert-butyl 4-bromo-2-methyl-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate
  参考文献：
  名称：

  [EN] 2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER
  [FR] DÉRIVÉS DE 2-CYANOISOINDOLINE POUR LE TRAITEMENT DU CANCER

  摘要：

  这项发明涉及公式I的新化合物，这些化合物是去泛素化酶（DUBs）和/或去泛素化酶的抑制剂。具体来说，该发明涉及抑制泛素C端水解酶7或泛素特异性肽酶7（USP7）。该发明还涉及这些化合物的制备方法以及它们在癌症治疗中的应用。

  公开号：

  WO2017158388A1
• 作为产物：
  描述：

  1-Boc-3-氰基-4-吡咯烷酮 在 甲酸铵 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以9.0 g的产率得到4-cyano-3-amino-1-(N-tert-butoxycarbonyl)-3,4-pyrroline
  参考文献：
  名称：

  [EN] 2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER
  [FR] DÉRIVÉS DE 2-CYANOISOINDOLINE POUR LE TRAITEMENT DU CANCER

  摘要：

  这项发明涉及公式I的新化合物，这些化合物是去泛素化酶（DUBs）和/或去泛素化酶的抑制剂。具体来说，该发明涉及抑制泛素C端水解酶7或泛素特异性肽酶7（USP7）。该发明还涉及这些化合物的制备方法以及它们在癌症治疗中的应用。

  公开号：

  WO2017158388A1

文献信息

• [EN] 6, 7 -DIHYDRO- 5H- PYRROLO [3, 4-D] PYRIMIDIN-4-YL] -QUINOLIN-3 -YLAMINE COMPOUNDS USEFUL AS FAAH MODULATORS AND USES THEREOF<br/>[FR] COMPOSÉS 6, 7 -DIHYDRO- 5H- PYRROLO [3, 4-D] PYRIMIDIN-4-YL] -QUINOLIN-3 -YLAMINE S'UTILISANT COMME MODULATEURS DE LA FAAH ET UTILISATIONS DESDITS COMPOSÉS
  申请人：RENOVIS INC

  公开号：WO2010059610A1

  公开（公告）日：2010-05-27

  Compounds are disclosed that have formula I: where A, B, L1, W, Y, R1, and R3 are as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non- limiting example, pain, anxiety, depression, inflammation, cognitive disorders, weight and eating disorders, Parkinson's disease, Alzheimer's disease, spasticity, addiction, glaucoma, and others.

  揭示了具有化学式I的化合物：其中A、B、L1、W、Y、R1和R3如本文所定义。这些化合物及其药物组成物对于哺乳动物包括人类的各种疾病的预防和治疗是有用的，包括但不限于疼痛、焦虑、抑郁、炎症、认知障碍、体重和进食障碍、帕金森病、阿尔茨海默病、痉挛、成瘾、青光眼等。
• Synthesis of the Intermediate of Gemifloxacin by the Chemoselective Hydrogenation of 4-Cyano-3-methoxyimino-1-(<i>N</i>-<i>tert</i>-butoxycarbonyl)pyrrolidine. Part 1. Screening of Metal Catalysts
  作者：Hyun Kuk Noh、Jae Sung Lee、Yeongdae Kim、Jay Hyok Chang、Hyunik Shin、Do Hyun Nam、Kyung Hee Lee

  DOI：10.1021/op049913u

  日期：2004.9.1

  methanesulfonate (AMPM), the key intermediate of gemifloxacin, based on chemoselective hydrogenation of the cyano group in 4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine (CMBP) with minimum reduction of the methyloxime group employing (t-Boc)2O (BOC) as in situ protecting agent. Over Raney nickel or cobalt catalysts, without in situ BOC protection of amine, the side reaction to 4-amino

  基于 4-cyano-3-methoxyimino-1-(N-tert) 中氰基的化学选择性加氢，设计了吉米沙星的关键中间体 4-aminomethyl-3-Z-methoxyiminopyrrolidine methanesulfonate (AMPM) 的新合成路线。 -丁氧基羰基）吡咯烷（CMBP），使用（t-Boc）2O（BOC）作为原位保护剂，甲基肟基团的还原最少。在阮内镍或钴催化剂上，在没有胺的原位 BOC 保护的情况下，通过甲基肟和氰基的同时氢化，生成 4-氨基甲基-3-氨基-1-(N-叔丁氧基羰基)吡咯烷 (AABP) 的副反应是广泛的CMBP 中的基团，导致所需中间体 4-氨基甲基-3-Z-甲氧基亚氨基 1-(N-叔丁氧基羰基)吡咯烷 (Z-AMBP) 一直过度还原为 AABP。当进行原位 BOC 保护时，
• COMPOUNDS USEFUL AS FAAH MODULATORS AND USES THEREOF
  申请人：Duncton Matthew

  公开号：US20110257208A1

  公开（公告）日：2011-10-20

  Compounds are disclosed that have formula I: where A, B, L 1 , W, Y, R 1 , and R 3 are as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, anxiety, depression, inflammation, cognitive disorders, weight and eating disorders, Parkinson's disease, Alzheimer's disease, spasticity, addiction, glaucoma, and others.

  公开了化学式为I的化合物，其中A、B、L1、W、Y、R1和R3的定义如本文所述。这些化合物及其制药组合物对于哺乳动物包括人类的各种疾病的预防和治疗有用，包括但不限于疼痛、焦虑、抑郁、炎症、认知障碍、体重和进食障碍、帕金森病、阿尔茨海默病、痉挛、成瘾、青光眼等。
• 2-cyanoisoindoline derivatives for treating cancer
  申请人：MISSION THERAPEUTICS LIMITED

  公开号：US10683269B2

  公开（公告）日：2020-06-16

  The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.

  本发明涉及式 I 的新型化合物，它们是去泛素化酶 (DUB) 和/或去umoylating 酶的抑制剂。特别是，本发明涉及对泛素 C 端水解酶 7 或泛素特异性肽酶 7（USP7）的抑制。本发明还涉及这些化合物的制备方法及其在治疗癌症中的用途。
• Synthesis of the Intermediate of Gemifloxacin by the Chemoselective Hydrogenation of 4-Cyano-3-methoxyimino-1-(<i>N</i><i>-tert</i>-butoxycarbonyl)pyrrolidine. Part 2. The Palladium Catalysts in Acidic Media
  作者：Hyun Kuk Noh、Jae Sung Lee、Yeongdae Kim、Gyohyun Hwang、Jay Hyok Chang、Hyunik Shin、Do Hyun Nam、Kyung Hee Lee

  DOI：10.1021/op0499122

  日期：2004.9.1

  Chemoselective hydrogenation of 4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine (CMBP) to 4-aminomethyl-3-Z-methoxyiminopyrrolidine methanesulfonate (AMPM), the key intermediate for gemifloxacin, was investigated over Pd catalysts with in situ acid protection. Addition of more than 1.6 equiv of acidic protons for CMBP was found to drastically elevate both the reaction rate and selectivity to 4-aminomethyl-3-Z-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine (Z-AMBP) over Pd catalyst with a complete suppression of the major side reaction to 4-cyano-3-amino-1-(N-tert-butoxycarbonyl)-3,4-pyrroline (CABP). Methanol as the organic solvent was found to increase the hydrogenation rate greatly compared to other solvents with a negligible decrease of selectivity. The leaching of Pd by acid and consequent accumulation of Pd ion in the reaction mixture was negligible in CMBP hydrogenation. The novel process of chemoselective CMBP hydrogenation in acidic media over Pd catalyst was thus much simpler yet more efficient compared to the conventional one. The whole AMPM process time starting from 1-(N-tert-butoxycarbonyl)-4-cyanopyrrolidine-3-one (BCPO) could be reduced by at least approximately 15 h which would result in a great reduction of materials such as catalysts, (t-Boc)(2)O, and solvent. Additionally, reduction of reaction steps improved the overall yield of AMPM significantly. Employment of methanesulfonic acid as an acidic agent in the hydrogenation step allowed an environmentally benign pathway to AMPM by omission of a neutralization step with an extra reduction in process time and materials consumed.