(-)-(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, dimethyl ester, 2,2-dioxide, hydrochloride | 1334399-59-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (-)-(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, dimethyl ester, 2,2-dioxide, hydrochloride
• 英文别名: dimethyl (1R,4S,5S,6S)-4-amino-2,2-dioxo-2lambda6-thiabicyclo[3.1.0]hexane-4,6-dicarboxylate;hydrochloride；dimethyl (1R,4S,5S,6S)-4-amino-2,2-dioxo-2λ6-thiabicyclo[3.1.0]hexane-4,6-dicarboxylate;hydrochloride
• CAS: 1334399-59-5
• 化学式: C₉H₁₃NO₆S*ClH
• 分子量: 299.732
• InChiKey: NMEBGOHZGCFXSC-YWJASCBZSA-N

物化性质

• 熔点：
  194 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -1.51
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (-)-(1'R,4S,5'S,6'S)-2,5-dioxospiro(imidazolidine-4,4'-[2]-thiabicyclo[3.1.0]hexane)-6'-carboxylic acid 2',2'-dioxide 在 三甲基氯硅烷 、 磷酸 、 水 、 氢溴酸 作用下， 反应 27.0h， 生成 (-)-(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, dimethyl ester, 2,2-dioxide, hydrochloride
  参考文献：
  名称：

  Process Development for a Key Synthetic Intermediate of LY2140023, a Clinical Candidate for the Treatment of Schizophrenia

  摘要：

  To fuel clinical development of the experimental CNS medicine LY2140023, we developed a scalable route for the multistep synthesis of a pivotal synthetic intermediate. The core of the conformationally restricted glutamic acid-based amino acid analogue was built via a Rh-catalyzed cyclopropanation of thiophene. Regioselective functionalization of the remaining double bond was achieved by a hydroboration/oxidation sequence followed by a Bucherer-Bergs reaction to give a hydantoin with the targeted L-glutamic acid configuration. Subsequent resolution, oxidation state, and protecting group manipulations gave the key intermediate in an overall nine-step scalable streamlined route starting from thiophene.

  DOI：

  10.1021/op100325h

文献信息

• Process Development for a Key Synthetic Intermediate of LY2140023, a Clinical Candidate for the Treatment of Schizophrenia
  作者：Mario Waser、Eric D. Moher、Sandy S. K. Borders、Marvin M. Hansen、David W. Hoard、Michael E. Laurila、Michael E. LeTourneau、Richard D. Miller、Michael L. Phillips、Kevin A. Sullivan、Jeffrey A. Ward、Chaoyu Xie、Cheryl A. Bye、Tanja Leitner、Brigitte Herzog-Krimbacher、Marcus Kordian、Martin Müllner

  DOI：10.1021/op100325h

  日期：2011.11.18

  To fuel clinical development of the experimental CNS medicine LY2140023, we developed a scalable route for the multistep synthesis of a pivotal synthetic intermediate. The core of the conformationally restricted glutamic acid-based amino acid analogue was built via a Rh-catalyzed cyclopropanation of thiophene. Regioselective functionalization of the remaining double bond was achieved by a hydroboration/oxidation sequence followed by a Bucherer-Bergs reaction to give a hydantoin with the targeted L-glutamic acid configuration. Subsequent resolution, oxidation state, and protecting group manipulations gave the key intermediate in an overall nine-step scalable streamlined route starting from thiophene.