4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine | 782479-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine
• 英文别名: tert-butyl 3-cyano-4-methoxyiminopyrrolidine-1-carboxylate
• CAS: 782479-64-5
• 化学式: C₁₁H₁₇N₃O₃
• 分子量: 239.274
• InChiKey: MQTBWSIGEFFPBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  368.5±52.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.38
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  74.92
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine 在 sodium hypobromide 、 碘代三甲硅烷 、 双氧水 、 sodium hydride 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 乙腈 为溶剂， 反应 11.17h， 生成 1-(2,4-difluorophenyl)-6-fluoro-7-[8-(methoxyimino)-1,6-diazaspiro[3.4]oct-6-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of naphthyridone derivatives containing 8-alkoxyimino-1,6-dizaspiro[3.4]octane scaffolds

  摘要：

  The synthesis of naphthyridone derivatives containing 8-alkoxyimino-1.6-dizaspiro[3.4]octane scaffolds, the position isomers of the side chain at the C-7 position of Zabofloxacin, has been achieved in eight steps from tert-butyl 3-cyano-4-oxopyrrolidine-1-carboxylate. The possible reaction mechanisms were also proposed. The key spirocyclic carbamate esters, which could be prepared using a modified Hofmann rearrangement strategy, were condensed with naphthyridone nuclei, and the resulting condensates were easily cleaved by TMSI and subsequently cyclized in the presence of K(2)CO(3). Moreover, additional N-methylation derivatives were also obtained using the synthetic sequence. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.08.089
• 作为产物：
  描述：

  甲氧基胺盐酸盐 、 1-Boc-3-氰基-4-吡咯烷酮 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.42h， 以43%的产率得到4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine
  参考文献：
  名称：

  含3-（N'-烷氧基氨基甲酰基）-4-（烷氧基亚氨基）吡咯烷的氟喹诺酮衍生物的合成及体外抗菌活性

  摘要：

  通过1 H NMR，MS和HRMS设计，合成和表征了一系列新颖的7- [3-（N'-烷氧基氨基甲酰基）-4-（烷氧基亚氨基）吡咯烷-1-基]氟喹诺酮衍生物。筛选这些氟喹诺酮类药物的体外抗菌活性。它们中的大多数在抑制金黄色葡萄球菌和表皮葡萄球菌的生长方面表现出良好的效力（MIC：0.06-4.00μg/ mL）。化合物33和43对金黄色葡萄球菌（包括MRSA和表皮葡萄球菌）的活性包括MRSE（MIC：0.06-0.125μg/ mL）在内的任何药物都比参考药物左氧氟沙星和吉非沙星更大或相当。此外，化合物33的效力分别比对照药物对屎肠球菌08-7和肺炎克雷伯菌的参考药物高32倍和16-32倍。

  DOI：

  10.1016/j.ejmech.2010.08.050

文献信息

• 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，
• 吉米沙星侧链化合物的制备方法
  申请人：北京阳光诺和药物研究股份有限公司

  公开号：CN113773240B

  公开（公告）日：2022-05-31

  本发明公开了一种吉米沙星侧链化合物的制备方法。所述制备方法包括如下步骤：S1、1‑N‑叔丁氧羰基‑4‑氰基‑3‑吡咯烷酮与甲氧基胺盐酸盐进行反应得到式(Ⅴ)所示化合物；S2、在惰性气氛中，在10～50℃的温度下、在钯碳存在的条件下，式(Ⅴ)所示化合物在0.1～0.5Mpa氢气氛围下进行加氢还原反应1～3h；再加入Boc酸酐，于10～50℃和0.1～0.5Mpa的条件下继续进行加氢还原反应4～8h，得到式(Ⅵ)所示化合物；S3、式(Ⅵ)所示化合物与酸反应脱除保护基，即得式(Ⅰ)所示吉米沙星侧链化合物。本发明制备方法，工艺简单，反应条件非常温和，很容易实现；(2)原料价格低廉，成本低；(3)开创一种新的、有效的吉米沙星侧链的合成工艺路线。
• 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.