6-bromo-5-methyl-3,4-dihydronaphthalene-2(1H)-one | 1337847-32-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-bromo-5-methyl-3,4-dihydronaphthalene-2(1H)-one
• 英文别名: 6-bromo-5-methyl-3,4-dihydronaphthalen-2(1H)-one；6-bromo-5-methyl-3,4-dihydro-1H-naphthalen-2-one
• CAS: 1337847-32-1
• 化学式: C₁₁H₁₁BrO
• 分子量: 239.112
• InChiKey: DAXYGTRTRNLQKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-(-)- α-甲基苄胺 、 6-bromo-5-methyl-3,4-dihydronaphthalene-2(1H)-one 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Regioisomerism in the Synthesis of a Chiral Aminotetralin Drug Compound: Unraveling Mechanistic Details and Diastereomer-Specific In-Depth NMR Investigations

  摘要：

  During chemical process development of a novel 2-aminotetralin derivative intended for use as an antidepressant, scrutiny of the byproduct present in the drug molecule revealed a set of regioisomers. Detailed studies showed that this impurity issue originated from an early synthetic step in which a brominated tetralone motif was generated in a ring-closing protocol. It was found that this reaction was accompanied by a migration of the aromatic bromo substituent via different bromonium species along two discrete pathways. This example of the halogen dance reaction resulted in the formation of a series of tetralone impurities with a bromine distributed across all available aromatic positions of the tetralin nucleus. Subsequently, when subjected to reductive amination conditions, each of these tetralones gave rise to pairs of aminotetralins in a diastereomeric relationship. NMR investigations revealed that the alicyclic portion of the compounds thus formed displayed very complex signal patterns, which required further in-depth studies using a variety of sophisticated techniques. As a result, a deep insight into the structural features of the current 2-aminotetralin family was obtained, which is emphasized by the definition of a novel "0.2 ppm rule" allowing the absolute configuration at tetralin C-2 to be determined.

  DOI：

  10.1021/jo300277y
• 作为产物：
  描述：

  3-甲基苯乙酸 在 aluminum (III) chloride 、 氯化亚砜 、 溴 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 6-bromo-5-methyl-3,4-dihydronaphthalene-2(1H)-one
  参考文献：
  名称：

  Regioisomerism in the Synthesis of a Chiral Aminotetralin Drug Compound: Unraveling Mechanistic Details and Diastereomer-Specific In-Depth NMR Investigations

  摘要：

  During chemical process development of a novel 2-aminotetralin derivative intended for use as an antidepressant, scrutiny of the byproduct present in the drug molecule revealed a set of regioisomers. Detailed studies showed that this impurity issue originated from an early synthetic step in which a brominated tetralone motif was generated in a ring-closing protocol. It was found that this reaction was accompanied by a migration of the aromatic bromo substituent via different bromonium species along two discrete pathways. This example of the halogen dance reaction resulted in the formation of a series of tetralone impurities with a bromine distributed across all available aromatic positions of the tetralin nucleus. Subsequently, when subjected to reductive amination conditions, each of these tetralones gave rise to pairs of aminotetralins in a diastereomeric relationship. NMR investigations revealed that the alicyclic portion of the compounds thus formed displayed very complex signal patterns, which required further in-depth studies using a variety of sophisticated techniques. As a result, a deep insight into the structural features of the current 2-aminotetralin family was obtained, which is emphasized by the definition of a novel "0.2 ppm rule" allowing the absolute configuration at tetralin C-2 to be determined.

  DOI：

  10.1021/jo300277y

文献信息

• [EN] CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS<br/>[FR] CARBOXAMIDES UTILISÉES EN TANT QU'INHIBITEURS DE PROTÉASE SPÉCIFIQUE DE L'UBIQUITINE
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2019032863A1

  公开（公告）日：2019-02-14

  The present disclosure relates to modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25, pharmaceutical compositions comprising the inhibitors, and methods of using the inhibitors. The modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25 can be useful in the treatment of cancers, among other ailments.

  本公开涉及调节剂，如抑制剂，至少选择自USP28和USP25中的一条途径的药物组合物包括这些抑制剂，以及使用这些抑制剂的方法。这些调节剂，如抑制剂，至少选择自USP28和USP25中的一条途径，可用于治疗癌症等疾病。
• Carboxamides as ubiquitin-specific protease inhibitors
  申请人：Valo Early Discovery, Inc.

  公开号：US11524966B1

  公开（公告）日：2022-12-13

  The present disclosure relates to modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25, pharmaceutical compositions comprising the inhibitors, and methods of using the inhibitors. The modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25 can be useful in the treatment of cancers, among other ailments.

  本公开涉及选自USP28和USP25的至少一种通路的调节剂（如抑制剂）、包含这些抑制剂的药物组合物以及使用这些抑制剂的方法。选自USP28和USP25的至少一种通路的调节剂（如抑制剂）可用于治疗癌症等疾病。
• CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS
  申请人：Forma Therapeutics, Inc.

  公开号：EP3665169A1

  公开（公告）日：2020-06-17
• [EN] CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS<br/>[FR] CARBOXAMIDES EN TANT QU'INHIBITEURS DE PROTÉASE SPÉCIFIQUES DE L'UBIQUITINE
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2020033707A1

  公开（公告）日：2020-02-13

  The present disclosure relates to modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25, pharmaceutical compositions comprising the inhibitors, and methods of using the inhibitors. The modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25 can be useful in the treatment of cancers, among other ailments.
• Regioisomerism in the Synthesis of a Chiral Aminotetralin Drug Compound: Unraveling Mechanistic Details and Diastereomer-Specific In-Depth NMR Investigations
  作者：Peter Schuisky、Hans-Jürgen Federsel、Wei Tian

  DOI：10.1021/jo300277y

  日期：2012.7.6

  During chemical process development of a novel 2-aminotetralin derivative intended for use as an antidepressant, scrutiny of the byproduct present in the drug molecule revealed a set of regioisomers. Detailed studies showed that this impurity issue originated from an early synthetic step in which a brominated tetralone motif was generated in a ring-closing protocol. It was found that this reaction was accompanied by a migration of the aromatic bromo substituent via different bromonium species along two discrete pathways. This example of the halogen dance reaction resulted in the formation of a series of tetralone impurities with a bromine distributed across all available aromatic positions of the tetralin nucleus. Subsequently, when subjected to reductive amination conditions, each of these tetralones gave rise to pairs of aminotetralins in a diastereomeric relationship. NMR investigations revealed that the alicyclic portion of the compounds thus formed displayed very complex signal patterns, which required further in-depth studies using a variety of sophisticated techniques. As a result, a deep insight into the structural features of the current 2-aminotetralin family was obtained, which is emphasized by the definition of a novel "0.2 ppm rule" allowing the absolute configuration at tetralin C-2 to be determined.