(S)-(+)-7-(2-chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one | 508169-20-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: (S)-(+)-7-(2-chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one
• 英文别名: (S)-5-(chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-7-oxo-5,6-dihydropyrrolo[3,4b]pyrazine；(S)-5-(chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-7-oxo-5,6-dihydropyrrolo[3,4-b]pyrazine；chloromethyl [(7S)-6-(5-chloropyridin-2-yl)-5-oxo-7H-pyrrolo[3,4-b]pyrazin-7-yl] carbonate
• CAS: 508169-20-8
• 化学式: C₁₃H₈Cl₂N₄O₄
• 分子量: 355.137
• InChiKey: LTLOOQRIMYDJAP-LBPRGKRZSA-N

物化性质

• 沸点：
  580.6±50.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  94.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 (S)-(+)-7-(2-chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one 以 丙酮 为溶剂， 反应 2.0h， 以90%的产率得到右佐匹克隆
  参考文献：
  名称：

  Optically active carbonates as precursors of (+)-zopiclone

  摘要：

  在本发明中，首次描述了式II的新化合物，其为对映富集形式，其中R1为氯代烷基。本发明还包括几种新的酶法过程，用于从相应的外消旋混合物中分离出式II的上述碳酸酯的对映体。将这些碳酸酯转化为对映富集的左西普克隆，构成了本发明的另一个方面。

  公开号：

  US06969767B1
• 作为产物：
  描述：

  6-(5-氯-2-吡啶基)-6,7-二氢-7-羟基-5H-吡咯并[3,4-b]吡嗪-5-酮 在 吡啶 、 phosphate buffer 、 Candida antarctica lipase B Chirazyme-L₂ 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 113.0h， 生成 (S)-(+)-7-(2-chloromethyloxycarbonyloxy)-6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one
  参考文献：
  名称：

  Enzymatic resolution of new carbonate intermediates for the synthesis of (S)-(+)-zopiclone

  摘要：

  The lipase from Candida antaretica B catalyzes the enantioselective hydrolysis of (+/-)-6-(5-chloropyridin-2-yl)-7-chloromethyloxycarbonyloxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one, a useful intermediate in the synthesis of (S)-(+)-zopiclone. This enzyme also catalyzes the resolution of the corresponding 2-chloroethylcarbonate derivative. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00685-7

文献信息

• Process for synthesis and purification of anhydrous crystalline S-zopiclone
  申请人：Apotecnia , S.A.

  公开号：EP2058313A3

  公开（公告）日：2009-06-24

  Process for synthesis and purification of anhydrous crystalline S-zopiclone for the preparation of enantiomerically pure S)-5-chloromethyloxycarbonyloxy)-6-5-chloropyrid-2-yl)-7-oxo-5,6-dihydropyrrolo[3,4b]pyrazine (S)-(I).

  合成和纯化无水结晶S-左西泮的过程，用于制备对映纯的(S)-5-(氯甲氧羰氧基)-6-(5-氯吡啶-2-基)-7-氧基-5,6-二氢吡咯并[3,4b]吡嗪(S)-(I)。
• Process for Preparation of Dextrorotatory Isomer of 6-(5- chloro-pyrid-2-yl)-5-[(4-methyl -1-piperazinyl) carbonyloxy] -7-oxo-6,7-dihydro-5H-pyrrolo [3,4-b] pyrazine (Eszopiclone)
  申请人：SATHE Dhananjay Govind

  公开号：US20090198058A1

  公开（公告）日：2009-08-06

  Disclosed herein is the process for preparation of 6-(5-chloro-pyrid-2-yl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (Zopiclone), its resolution to get the dextrorotatory isomer of formula (I) substantially free of R(−) enantiomer and recovery of key raw material i.e. 6-(5-chloro pyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo[3,4-b]pyrazine from the R-isomer of Zopiclone followed by conversion of the recovered compound to get pure Eszopiclone (I) in high yield and high purity.

  本发明涉及制备6-（5-氯吡啶-2-基）-5-[(4-甲基-1-哌嗪基)羰氧基]-7-氧代-6,7-二氢-5H-吡咯并[3,4-b]吡嗪（Zopiclone）的过程，其分离获得公式（I）右旋异构体，基本上不含R（-）对映体，以及从Zopiclone的R-异构体中恢复关键原料，即6-（5-氯吡啶-2-基）-5-羟基-7-氧代-5,6-二氢-吡咯并[3,4-b]吡嗪，随后将恢复的化合物转化为高产率和高纯度的纯Eszopiclone（I）。
• Resolution of (±)-5-substituted-6-(5-chloropyridin-2-yl)-7-oxo-5,6-dihydropyrrolo[3,4b]pyrazine derivatives-precursors of (S)-(+)-Zopiclone, catalyzed by immobilized Candida antarctica B lipase in aqueous media
  作者：Jose M Palomo、Cesar Mateo、Gloria Fernández-Lorente、Laura F Solares、Monica Diaz、Vı́ctor M Sánchez、Miguel Bayod、Vicente Gotor、Jose M Guisan、Roberto Fernandez-Lafuente

  DOI：10.1016/s0957-4166(02)00867-4

  日期：2003.2

  The enzymatic resolution of different cyclopyrrolone compounds has been performed in aqueous systems using different immobilized preparations of lipase from Candida antarctica (fraction B). The relevance of the immobilizaition protocol in the results has been shown: lipase immobilized on octadecyl-Sepabeads gave the highest stability and enantioselectivity. Commercial Novozym 435 was scarcely enantioselective in the hydrolytic process. On the other hand, the structure of the cyclopyrrolone was also found to be very important to the outcome of the reaction, the best results being achieved with compounds (+/-)-l and (+/-)-2. Thus. using compound (+/-)-2. a ee(s) of < 95% can be achieved under conditions in which the enzyme preparation can be utilized in 10 recycles without any significant detriment to the enzymatic properties (activity, enantioselectivity). Moreover, this enzyme catalyzes the hydrolytic resolution of chloromethyl carbonate (+/-)-5, a useful intermediate for the synthesis of the hypnotic agent (S)-(+)-Zopiclone. (C) 2003 Elsevier Science Ltd. All rights reserved.
• US6969767B1
  申请人：——

  公开号：US6969767B1

  公开（公告）日：2005-11-29
• Enzymatic resolution of new carbonate intermediates for the synthesis of (S)-(+)-zopiclone
  作者：Laura F. Solares、Mónica Dı́az、Rosario Brieva、Vı́ctor M. Sánchez、Miguel Bayod、Vicente Gotor

  DOI：10.1016/s0957-4166(02)00685-7

  日期：2002.11

  The lipase from Candida antaretica B catalyzes the enantioselective hydrolysis of (+/-)-6-(5-chloropyridin-2-yl)-7-chloromethyloxycarbonyloxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one, a useful intermediate in the synthesis of (S)-(+)-zopiclone. This enzyme also catalyzes the resolution of the corresponding 2-chloroethylcarbonate derivative. (C) 2002 Elsevier Science Ltd. All rights reserved.