2-氨基-5-溴-6-甲基-4(1H)-喹唑啉酮 | 147149-89-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-氨基-5-溴-6-甲基-4(1H)-喹唑啉酮
• 中文别名: 8-硝基-7-甲基氨基喹啉
• 英文名称: 2-amino-5-bromo-6-methyl-3-H-quinazolin-4-one
• 英文别名: 2-amino-5-bromo-6-methyl-3H-quinazolin-4-one；(8)-2-Amino-5-bromo-3,4-di-hydro-6-methylquinazolin-4-one；2-Amino-5-bromo-6-methylquinazolin-4(3H)-one
• CAS: 147149-89-1
• 化学式: C₉H₈BrN₃O
• 分子量: 254.086
• InChiKey: NLYAFCDSBNSHPU-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  450.0±55.0 °C(Predicted)
• 密度：
  1.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  吡啶-4(1H)-硫酮 、 2-氨基-5-溴-6-甲基-4(1H)-喹唑啉酮 在 copper(I) oxide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 以84%的产率得到诺拉曲特
  参考文献：
  名称：

  A Large Scale Process for the Preparation of Thymitaq

  摘要：

  The large scale manufacturing of the anticancer agent 2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)-3H-quinazolin-4-one dihydrochloride (thymitaq) from 6-bromo-5-methylanthranilic acid is described. The chemical route consists of two chemical steps: formation of a bromoquinazolinone and a copper-mediated Ullman-like coupling between 4-mercaptopyridine and the bromoquinazolinone. During process development, sodium hydride was replaced with sodium hydroxide and a method for removal of copper, based on 2,4,6-trimercapto-s-triazine, was developed. A number of purification operations were performed to ensure a product of pharmaceutical quality.

  DOI：

  10.1021/op800181e
• 作为产物：
  描述：

  2-氨基-6-溴-5-甲基苯甲酸 在 氢氧化钾 、 硫酸 作用下， 以 水 、 乙二醇 为溶剂， 反应 0.33h， 生成 2-氨基-5-溴-6-甲基-4(1H)-喹唑啉酮
  参考文献：
  名称：

  New Straightforward Synthesis of2‐Amino‐6‐methyl‐5‐(pyridin‐4‐ylsulfanyl)‐3H‐quinazolin‐4‐one

  摘要：

  The synthesis of 2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)-3H-quinazolin-4-one (1) was studied via three different synthetic routes starting from 4-bromo-5-methylisatin. The best route was established, which is a straightforward route via 2-guanidino-5-bromo-6-methyl-quinazolin-4-one (6) as the key intermediate and a one-pot synthesis by treatment of compound 6 with 4-mercaptopyridine and KOH via the Ullmann reaction. When removing the amidino group from 2-guanyl of compound 6 under strong alkaline conditions, surprisingly we found that 4-mercaptopyridine could prevent the bromo group on a quinazoline ring from substitution by a hydroxyl group. Furthermore we found that 4-mercaptopyridine analogues such as hydroxypyridinones also play a role of protecting agent in such a reaction system.

  DOI：

  10.1080/00397910600978085

文献信息

• Pyridine-4-thiol and Amphoteric Analogs: Novel Protection of Aryl Bromides in Strong Alkali
  作者：Wei-Min Chen、Chao Cheng、Bing-Zhou Li、Tse-Lok Ho、Zhao-Shuo Cai、Yuqiang Wang、Ping-Hua Sun

  DOI：10.1002/hlca.200890219

  日期：2008.11

  The use of pyridine-4-thiol (PT) to preserve certain aryl bromides in strong alkali is reported (Scheme 1). The presence of this additive or of some of its amphoteric analogs such as 3-hydroxypyridin-4(1H)-ones suppresses the replacement of the Br-substituent by hydroxide and alkoxide ions. A mechanistic interpretation of the effect is proposed.

  据报道使用吡啶-4-硫醇（PT）在强碱中保存某些芳基溴化物（方案1）。该添加剂或其某些两性类似物（例如3-羟基吡啶-4（1 H）-ones）的存在抑制了氢氧根和烷氧基离子对Br取代基的取代。提出了对该效应的机械解释。
• [EN] ANTIPROLIFERATIVE QUINAZOLINES<br/>[FR] QUINAZOLINES ANTI-PROLIFERATIVES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1993020055A1

  公开（公告）日：1993-10-14

  (EN) Quinazoline compounds which demonstrate antiproliferative activity, such as antitumor activity, processes of preparing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds. These compounds inhibit the growth and proliferation of the cells of higher organisms and microorganisms, such as bacteria, yeasts and fungi. Preferred quinazoline compounds are capable of inhibiting the enzyme thymidylate synthase. Effects derived from the inhibition of the enzyme thymidylate synthase include those discussed above.(FR) On décrit des composés de quinazoline qui manifestent une activité anti-proliférative telle qu'une activité anti-tumorale, des procédés permettant de préparer ces composés, des compositions pharmaceutiques qui les contiennent, ainsi que l'utilisation desdits composés. Ces derniers inhibent la croissance et la prolifération de cellules chez les organismes supérieurs et les micro-organismes tels que les bactéries, les levures et les champignons. Des composés de quinazoline préférés sont en mesure d'inhiber une enzyme, la thymidylate synthase. Les effets provenant de cette inhibition de la thymidylate synthase incluent ceux mentionnés ci-dessus.

  (中) 描述了一种表现出抗增殖活性，如抗肿瘤活性的喹唑啉化合物，以及制备这些化合物的过程，含有这些化合物的药物组合物，以及这些化合物的用途。这些化合物抑制高等生物和微生物（如细菌，酵母菌和真菌）的细胞生长和增殖。优选的喹唑啉化合物能够抑制胸腺嘧啶合成酶酶。由抑制胸腺嘧啶合成酶酶产生的效应包括上述讨论的效应。
• Org. Process Res. Dev. 2008, 12, 1195-1200
  作者：

  DOI：——

  日期：——
• Chemical Reagents 2011, 33, 1131-1134
  作者：

  DOI：——

  日期：——
• ANTIPROLIFERATIVE QUINAZOLINES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP0637300A1

  公开（公告）日：1995-02-08