4-(7-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester | 846032-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(7-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(7-fluoronaphthalen-1-yl)piperazine-1-carboxylate；4-(7-fluoronaphthalen-1-yl)piperazine-1-carboxylic acid tert-butyl ester
• CAS: 846032-49-3
• 化学式: C₁₉H₂₃FN₂O₂
• 分子量: 330.402
• InChiKey: PRDUYIZZSDXDKK-UHFFFAOYSA-N

物化性质

• 沸点：
  461.3±35.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(7-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 乙醇 、 甲苯 为溶剂， 以97 g的产率得到1-(7-fluoro-naphthalen-1-yl)-piperazine hydrochloride
  参考文献：
  名称：

  1-(7-氟-萘-1-基)哌嗪盐酸盐的实用合成

  摘要：

  摘要 报道了 1-(7-fluoronaphthalen-1-yl)-哌嗪盐酸盐 (1) 的实用且可扩展的制备方法。该化合物的原始合成路线涉及使用 1-氨基-7-氟萘和双（2-氯乙基）胺盐酸盐，这两种剧毒化合物。已开发出一种新方案，该方案采用钯催化的 1-Boc-哌嗪和 1-溴-7-氟萘之间的 Buchwald-Hartwig 交叉偶联反应，然后用 HCl 气体对哌嗪脱保护。此外，有效的钯去除方案允许制备含有少于 20 ppm 这种金属的目标分子。该方法已成功实施以生产多克数量的具有优异纯度和低钯含量的 1。

  DOI：

  10.1080/00397910802179979
• 作为产物：
  描述：

  7-氟萘-1-醇 在 palladium diacetate 、 三乙胺 、 sodium t-butanolate 、 2-(二环己基膦基)联苯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 4-(7-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of monofluorinated 1-(naphthalen-1-yl)piperazines

  摘要：

  A series of regioisomerically monofluorinated 1-(naplithaten-1-yl)piperazines is described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.05.156

文献信息

• [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
  申请人：Clark D. Jerry

  公开号：US20050043309A1

  公开（公告）日：2005-02-24

  This invention relates to compounds of the formula 1 wherein G, D, A, Z, Q, X, Y, R 1 , and R 4 through R 7 are defined as in the specification, processes for preparing the same and intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.

  这项发明涉及公式1的化合物 其中G、D、A、Z、Q、X、Y、R 1 和R 4 至R 7 的定义如规范中所述，制备这些化合物的方法以及用于制备这些化合物的中间体，以及含有这些化合物的药物组合物及其在治疗中枢神经系统疾病和其他疾病中的用途。
• [EN] [1,8]NAPHTHYRIDIN-2-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA<br/>[FR] [1,8]NAPHTYRIDIN-2-ONES ET COMPOSES APPARENTES DESTINES AU TRAITEMENT DE LA SCHIZOPHRENIE
  申请人：WARNER LAMBERT CO

  公开号：WO2005019215A1

  公开（公告）日：2005-03-03

  This invention relates to compounds of the Formula (1) wherein G, A, Z, Q, X, Y, and R1 and R2 are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system and other disorders.

  本发明涉及式（1）的化合物，其中G，A，Z，Q，X，Y和R1和R2如规范中所定义，包含它们的制药组合物以及它们在治疗中枢神经系统和其他疾病中的应用。
• [1,8]NAPHTHYRIDIN-2-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA
  申请人：Clark D. Jerry

  公开号：US20060287310A1

  公开（公告）日：2006-12-21

  This invention relates to compounds of the formula 1 wherein G, D, A, Z, Q, X, Y, R 1 , and R 4 through R 7 are defined as in the specification, processes for preparing the same and intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.

  本发明涉及式1的化合物，其中G、D、A、Z、Q、X、Y、R1和R4至R7如规范中所定义，制备该化合物的过程以及用于制备该化合物的中间体，以及含有该化合物的制药组合物及其在治疗中枢神经系统疾病和其他疾病中的应用。
• The Synthesis of a Dopamine D₂ Partial Agonist for the Treatment of Schizophrenia
  作者：Javier Magano、Alison Acciacca、Anne Akin、Benjamin M. Collman、Brian Conway、Michael Waldo、Michael H. Chen、Kenneth E. Mennen

  DOI：10.1021/op800307k

  日期：2009.5.15

  The synthesis of the phosphoric acid salt of dopamine D-2 partial agonist 2-4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8- one (1) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO4. The optimized synthetic route for the preparation of phosphate salt I consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13. Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude material with the required purity, suitable for use in the subsequent salt formation step. Finally, considerable work was carried out to determine the most stable polymorph of the API. As a result, a robust set of conditions has been developed for the formation of phosphoric acid salt 1, providing the desired polymorph in excellent yield and purity.
• WO2007/116265
  申请人：——

  公开号：——

  公开（公告）日：——