N-cyclopropyl-3-(1-hydroxyphthalazin-6-yl)-4-methylbenzamide | 909189-26-0

• 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: N-cyclopropyl-3-(1-hydroxyphthalazin-6-yl)-4-methylbenzamide
• 英文别名: N-cyclopropyl-4-methyl-3-(1-oxo-2H-phthalazin-6-yl)benzamide
• CAS: 909189-26-0
• 化学式: C₁₉H₁₇N₃O₂
• 分子量: 319.363
• InChiKey: RNOKCJDQOOPMRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  70.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-cyclopropyl-3-(1-hydroxyphthalazin-6-yl)-4-methylbenzamide 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(1-chloro-6-phthalazinyl)-N-cyclopropyl-4-methylbenzamide 、 、
  参考文献：
  名称：

  Practical Synthesis of a p38 MAP Kinase Inhibitor

  摘要：

  p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.

  DOI：

  10.1021/jo802186m
• 作为产物：
  描述：

  、 环丙胺 以 1,2-二氯乙烷 为溶剂， 以0.27 g的产率得到N-cyclopropyl-3-(1-hydroxyphthalazin-6-yl)-4-methylbenzamide
  参考文献：
  名称：

  Practical Synthesis of a p38 MAP Kinase Inhibitor

  摘要：

  p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.

  DOI：

  10.1021/jo802186m

文献信息

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

  公开号：US20060199817A1

  公开（公告）日：2006-09-07

  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.

  本发明包括一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症及相关状况。这些化合物的通用公式为I 其中A 1 ，A 2 ，B，R 1 ，R 2 ，R 3 和R 4 在此定义。该发明还包括包括一个或多个I公式化合物的药物组合物，以及使用这些化合物和组合物治疗激酶介导的疾病，包括类风湿性关节炎，银屑病和其他炎症性疾病，以及用于制备I公式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：EP1856058B1

  公开（公告）日：2014-09-03
• US7759337B2
  申请人：——

  公开号：US7759337B2

  公开（公告）日：2010-07-20
• [EN] PHTHALAZINE, AZA- AND DIAZA-PHTHALAZINE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES DE PHTHALAZINE, AZA- ET DIAZA-PHTHALAZINE ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：AMGEN INC

  公开号：WO2006094187A2

  公开（公告）日：2006-09-08

  [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] L'invention concerne une classe de composés utiles dans la prophylaxie et le traitement de maladies induites par les protéines kinases, notamment des inflammations et des états relatifs. Les composés sont de formule générale I, dans laquelle A1, A2, B, R1, R2, R3 et R4 sont définis dans la description. L'invention concerne également des compostions pharmaceutiques renfermant un ou plusieurs composés de formule I, des utilisations de ces composés et compositions dans le traitement de maladies induites par les protéines kinases, notamment l'arthrite rhumatoïde, le psoriasis et d'autres troubles inflammatoires, des intermédiaires et des procédés utiles dans la préparation des composés de formule I.
• Practical Synthesis of a p38 MAP Kinase Inhibitor
  作者：Michał Achmatowicz、Oliver R. Thiel、Philip Wheeler、Charles Bernard、Jinkun Huang、Robert D. Larsen、Margaret M. Faul

  DOI：10.1021/jo802186m

  日期：2009.1.16

  p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.