6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine | 1114530-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine
• 英文别名: Phthalazine, 6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)-；6-chloro-1-(1,1,1-trifluoropropan-2-yloxy)phthalazine
• CAS: 1114530-32-3
• 化学式: C₁₁H₈ClF₃N₂O
• 分子量: 276.646
• InChiKey: IEQHLQKPMXLMPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine 生成 (R)-6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine 、 (S)-6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine
  参考文献：
  名称：

  Development of a Practical Synthesis of a p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the phthalazine-based p38 MAP kinase inhibitor [(S)-2] was needed for an ongoing program. Vibrational circular dichroism provided the assignment of the absolute stereochemistry of the target compound. The selected synthetic route for (S)-2 required identification of efficient reaction conditions for the construction of carbon-oxygen, carbon-carbon, and carbon-nitrogen bonds to connect the key building blocks. An efficient two-step method (chlorodehydroxylation, aromatic nucleophilic substitution) for the synthesis of arylether [(S)-10] was developed. PAT (in situ Raman spectroscopy) was utilized to monitor and control the formation of a lithium alkoxide in this reaction. The synthesis of (S)-2 was completed using high-yielding Suzuki- and amide-coupling reactions. The isolation conditions for these steps were optimized to obtain material of very high purity without the need for any complicated workup procedures.

  DOI：

  10.1021/op800250v
• 作为产物：
  描述：

  1,6-二氯-二氮杂萘 、 1,1,1-三氟异丙醇 在 正丁基锂 作用下， 以 正己烷 、 甲基叔丁基醚 为溶剂， 反应 1.5h， 以78%的产率得到6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine
  参考文献：
  名称：

  Development of a Practical Synthesis of a p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the phthalazine-based p38 MAP kinase inhibitor [(S)-2] was needed for an ongoing program. Vibrational circular dichroism provided the assignment of the absolute stereochemistry of the target compound. The selected synthetic route for (S)-2 required identification of efficient reaction conditions for the construction of carbon-oxygen, carbon-carbon, and carbon-nitrogen bonds to connect the key building blocks. An efficient two-step method (chlorodehydroxylation, aromatic nucleophilic substitution) for the synthesis of arylether [(S)-10] was developed. PAT (in situ Raman spectroscopy) was utilized to monitor and control the formation of a lithium alkoxide in this reaction. The synthesis of (S)-2 was completed using high-yielding Suzuki- and amide-coupling reactions. The isolation conditions for these steps were optimized to obtain material of very high purity without the need for any complicated workup procedures.

  DOI：

  10.1021/op800250v

文献信息

• Phthalazine, aza-and diaza-phthalazine compounds and methods of use
  申请人：Tasker Andrew

  公开号：US20080119468A1

  公开（公告）日：2008-05-22

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , B, R 1 , R 2 , R 3 and R 4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新型化合物类别，用于预防和治疗蛋白激酶介导的疾病，包括炎症及相关病症。该化合物具有一般式I，其中A1、A2、B、R1、R2、R3和R4在此定义。本发明还包括含有一种或多种式I化合物的制药组合物，以及用于治疗激酶介导的疾病，包括类风湿性关节炎、牛皮癣和其他炎症性疾病的该化合物和组合物的用途，以及用于制备式I化合物的中间体和方法。
• Phthalazine compounds and methods of use
  申请人：Amgen Inc.

  公开号：US08101612B2

  公开（公告）日：2012-01-24

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of p38 kinase mediated diseases and related inflammatory conditions. The compounds have a general Formula II wherein L1, L2, R1a, R1b, R1c, R2, R3, R3a, R4, R5 and p are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of p38 kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新的化合物类别，用于预防和治疗p38激酶介导的疾病和相关的炎症状况。这些化合物具有通用的公式II，其中L1、L2、R1a、R1b、R1c、R2、R3、R3a、R4、R5和p的定义在此处。本发明还包括制药组合物，包括一个或多个公式I化合物，以及这些化合物和组合物用于治疗p38激酶介导的疾病，包括类风湿性关节炎、牛皮癣和其他炎症性疾病，以及用于制备公式I化合物的中间体和工艺。
• PHTHALAZINE, AZA- AND DIAZA-PHTHALAZINE COMPOUNDS AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：EP2077998B1

  公开（公告）日：2011-03-09
• US8101612B2
  申请人：——

  公开号：US8101612B2

  公开（公告）日：2012-01-24
• [EN] PHTHALAZINE, AZA- AND DIAZA-PHTHALAZINE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS DE PHTALAZINE, D'AZA-PHTALAZINE ET DE DIAZA-PHTALAZINE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2008030466A1

  公开（公告）日：2008-03-13

  [EN] The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A¹, A², B, R¹, R², R³ and R⁴ are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.
  [FR] La présente invention concerne une nouvelle classe de composés utilisables pour la prophylaxie et le traitement de maladies induites par la protéine-kinase, y compris l'inflammation et les affections apparentées. Les composés répondent à la formule générale (I) [INSÉRER LA STRUCTURE ICI] (I) dans laquelle A¹, A², B, R¹, R², R³ et R⁴ sont définis ici. L'invention concerne également des compositions pharmaceutiques qui comprennent un ou plusieurs composés de formule (I), l'utilisation de tels composés et de telles compositions pour le traitement de maladies induites par la protéine-kinase, y compris la polyarthrite rhumatoïde, le psoriasis et d'autres affections inflammatoires, ainsi que des intermédiaires et des procédés utilisables pour la préparation de composés de formule (I).