6-[(4-Chloro-phenylamino)-methyl]-5-methyl-quinazoline-2,4-diamine; compound with acetic acid | 52128-30-0

• 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: 6-[(4-Chloro-phenylamino)-methyl]-5-methyl-quinazoline-2,4-diamine; compound with acetic acid
• 英文别名: Acetic acid;6-[(4-chloroanilino)methyl]-5-methylquinazoline-2,4-diamine；acetic acid;6-[(4-chloroanilino)methyl]-5-methylquinazoline-2,4-diamine
• CAS: 52128-30-0
• 化学式: C₂H₄O₂*C₁₆H₁₆ClN₅
• 分子量: 373.842
• InChiKey: SOGFUVSMMNCSOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  127
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对氯苯胺 、 溶剂黄146 、 2,4-二氨基-5-甲基喹唑啉-6-甲腈 在 镍 氢气 作用下， 28.0 ℃ 、344.73 kPa 条件下， 反应 22.0h， 以13%的产率得到6-[(4-Chloro-phenylamino)-methyl]-5-methyl-quinazoline-2,4-diamine; compound with acetic acid
  参考文献：
  名称：

  Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino)methyl]-2,4-quinazolinediamines

  摘要：

  A series of 6-[(arylamino)methyl]-2,4-quinazolinediamines have been prepared by catalytic hydrogenation of the requisite 2,4-diamino-6-quinazolinecarbonitriles in the presence of the appropriate benzenamine. Formylation, acetylation, and nitrosation provided N omega derivatives of these compounds. A variety of the compounds exhibited potent antimalarial, antibacterial, and antitumor activity. In particular, 5-methyl-6-[[(3,4,5-trimethoxyphenyl)-amino]methyl]-2, 4-quinazolinediamine (trimetrexate, 15) has shown a broad spectrum of antitumor effects and is undergoing preclinical toxicology evaluation prior to trial in man.

  DOI：

  10.1021/jm00366a018

文献信息

• Process for preparing 5,6-substituted-2,4-quinazolinediamines and intermediates
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0253396A2

  公开（公告）日：1988-01-20

  An improved process for the preparation of 6-substituted-5-­alkyl-2,4-quinazolinediamines, useful in the production of trimetrexate and similar antifolate agents, together with several novel intermediates are disclosed.

  本发明公开了一种改进的 6-取代-5-烷基-2,4-喹唑啉二胺制备工艺以及几种新型中间体，该工艺可用于生产曲美曲塞特和类似的抗叶酸制剂。
• Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino)methyl]-2,4-quinazolinediamines
  作者：Edward F. Elslager、Judith L. Johnson、Leslie M. Werbel

  DOI：10.1021/jm00366a018

  日期：1983.12

  A series of 6-[(arylamino)methyl]-2,4-quinazolinediamines have been prepared by catalytic hydrogenation of the requisite 2,4-diamino-6-quinazolinecarbonitriles in the presence of the appropriate benzenamine. Formylation, acetylation, and nitrosation provided N omega derivatives of these compounds. A variety of the compounds exhibited potent antimalarial, antibacterial, and antitumor activity. In particular, 5-methyl-6-[[(3,4,5-trimethoxyphenyl)-amino]methyl]-2, 4-quinazolinediamine (trimetrexate, 15) has shown a broad spectrum of antitumor effects and is undergoing preclinical toxicology evaluation prior to trial in man.