2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one | 911415-80-0

• 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: 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one
• 英文别名: 8-[4-[4-(7-fluoronaphthalen-1-yl)piperazin-1-yl]butoxy]-1,3,4,5-tetrahydropyrido[2,3-d][1,3]diazepin-2-one
• CAS: 911415-80-0
• 化学式: C₂₆H₃₀FN₅O₂
• 分子量: 463.555
• InChiKey: XBWYOLGEGJFFRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  69.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one 在 磷酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 0.33h， 以87%的产率得到2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one phosphoric acid salt
  参考文献：
  名称：

  The Synthesis of a Dopamine D₂ Partial Agonist for the Treatment of Schizophrenia

  摘要：

  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.

  DOI：

  10.1021/op800307k
• 作为产物：
  描述：

  4-(7-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 、 甲醇 、 potassium carbonate 作用下， 以 甲基叔丁基醚 、 水 、 乙腈 为溶剂， 反应 23.0h， 生成 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one
  参考文献：
  名称：

  WO2007/116265

  摘要：

  公开号：

文献信息

• Substituted biaryl amides as C5A receptor modulators
  申请人：Gao Yang

  公开号：US20050096358A1

  公开（公告）日：2005-05-05

  Substituted biaryl amides of Formula I are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5a receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了式I的取代联芳酰胺化合物。这些化合物是配体，可用于在体内或体外调节C5a受体活性，并且在治疗与人类、家畜伴侣动物和家畜动物中的C5a受体病理性激活相关的情况中特别有用。提供了用于治疗此类疾病的制药组合物和方法，以及用于受体定位研究的这种配体的使用方法。
• Substituted biaryl amides as C5a receptor modulators
  申请人：Gao Yang

  公开号：US20060178414A1

  公开（公告）日：2006-08-10

  Substituted biaryl amides of Formula I are provided. Such compounds are ligands that may be used to modulate C5 a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5 a receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  提供了公式I的取代联苯酰胺化合物。这些化合物是配体，可用于体内或体外调节C5a受体活性，并且在治疗与人类、家养伴侣动物和家畜动物的病理性C5a受体激活相关的疾病方面特别有用。提供了用于治疗此类疾病的制药组合物和方法，以及用于受体定位研究的此类配体的使用方法。
• Tetrahydro-pyridoazepin-8-ones and related compounds for the treatment of schizophrenia
  申请人：Favor David

  公开号：US20060234997A1

  公开（公告）日：2006-10-19

  Compounds of formula 1 are disclosed, wherein G, D, A, Q, Y, Z, and R 1 through R 10 are defined in the specification. Also provided are descriptions of processes for preparing compounds of formula 1, 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.

  本文披露了化学式1的化合物，其中G、D、A、Q、Y、Z和R1至R10在说明书中有定义。还提供了制备化学式1的过程的描述，用于制备化合物的中间体，以及含有这些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。
• テトラヒドロ−ピリドアゼピン−８−オン化合物を製造する方法
  申请人：ファイザー・プロダクツ・インク

  公开号：JP2007269796A

  公开（公告）日：2007-10-18

  【課題】テトラヒドロ−ピリドアゼピン−８−オン化合物を製造する方法【解決手段】本発明は、２−｛４−［４−（７−フルオロ−ナフタレン−１−イル）−ピペラジン−１−イル］−ブトキシ｝−５，６，７，９−テトラヒドロ−１，７，９−トリアザ−ベンゾシクロヘプテン−８−オンを製造する方法に関する。該方法は、１−（７−フルオロ−ナフタレン−１−イル）−ピペラジン塩酸塩を式（ＩＩ）：｛ここで、式（ＩＩ）のＬは、脱離基である｝で表される化合物と反応させることを含む。【選択図】なし

  4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-四氢-1,7,9-三氮杂苯并环庚烯-8-酮。该方法涉及生产 1-(7-丁氧基)-苯并环庚烯-8-酮的方法。该方法涉及生产由式(II)表示的 1-(7-氟-1-萘基)-哌嗪盐酸盐：式(II)中 L 为离去基团}，其中式(II)中 L 为离去基团。式（II）中的 L 为离去基团。无。
• TETRAHYDRO-PYRIDOAZEPIN-8-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA
  申请人：Warner-Lambert Company LLC

  公开号：EP1869041A1

  公开（公告）日：2007-12-26