(6-iodoquinazolin-4-yl)-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine hydrochloride | 537705-10-5

• 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-iodoquinazolin-4-yl)-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine hydrochloride
• 英文别名: 4-Quinazolinamine,6-iodo-n-[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]-,hydrochloride；6-iodo-N-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazolin-4-amine;hydrochloride
• CAS: 537705-10-5
• 化学式: C₂₁H₁₇IN₄O*ClH
• 分子量: 504.758
• InChiKey: IREWPHJJTYVXQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  59.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6-iodoquinazolin-4-yl)-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine hydrochloride 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 32.0h， 生成 E-2-methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide dimesylate
  参考文献：
  名称：

  Evaluation of Kilogram-Scale Sonagashira, Suzuki, and Heck Coupling Routes to Oncology Candidate CP-724,714

  摘要：

  The synthesis of the anti-cancer compound 2-methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)phenylamino]quinazolin-6-yl}-E-allyl)acetamide (CP-724,714) (1) on multikilogram scale using several different synthetic routes is described. Application of the Sonogashira, Suzuki, and Heck couplings to this synthesis was investigated to identify a safe, environmentally friendly, and robust process for the production of this drug candidate. A convergent and selective synthesis of the candidate was identified which utilizes a Heck coupling of a protected allylamine to install the critical olefin.

  DOI：

  10.1021/op050039u
• 作为产物：
  描述：

  6-碘-4(H)-喹唑啉酮 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 2.0h， 生成 (6-iodoquinazolin-4-yl)-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine hydrochloride
  参考文献：
  名称：

  Evaluation of Kilogram-Scale Sonagashira, Suzuki, and Heck Coupling Routes to Oncology Candidate CP-724,714

  摘要：

  The synthesis of the anti-cancer compound 2-methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)phenylamino]quinazolin-6-yl}-E-allyl)acetamide (CP-724,714) (1) on multikilogram scale using several different synthetic routes is described. Application of the Sonogashira, Suzuki, and Heck couplings to this synthesis was investigated to identify a safe, environmentally friendly, and robust process for the production of this drug candidate. A convergent and selective synthesis of the candidate was identified which utilizes a Heck coupling of a protected allylamine to install the critical olefin.

  DOI：

  10.1021/op050039u

文献信息

• Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors
  申请人：Wallace Eli

  公开号：US20050101617A1

  公开（公告）日：2005-05-12

  Cyanoguanidine quinazoline and cyanoamidine quinazolamine derivatives that are useful in the treatment of hyperproliferative diseases are disclosed. Methods of treating hyperproliferative diseases in mammals are also disclosed.

  本文披露了在治疗过度增殖性疾病中有用的氰胍嘧啶和氰胍胺喹唑啉衍生物。还披露了在哺乳动物中治疗过度增殖性疾病的方法。
• [EN] PROCESSES FOR THE PREPARATION OF N-((((PYRIDINYLOXY) -PHENYLAMINO) QUINAZOLINYL)- ALLYL) ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS WELL AS INTERMEDIATES OF SUCH PROCESSES AND PROCESSES FOR THE PREPARATION OF SUCH INTERMEDIATES<br/>[FR] PROCEDES DE PREPARATION DE DERIVES DE N-((((PYRIDINYLOXY) -PHENYLAMINO) QUINAZOLINYL)- ALLYL) ACETAMIDE ET DES COMPOSES APPARENTES ET INTERMEDIAIRES POUR CES PROCEDES ET PROCEDES DE PREPARATION DE CES INTERMEDIAIRES
  申请人：PFIZER PROD INC

  公开号：WO2004089934A1

  公开（公告）日：2004-10-21

  The invention relates to processes for preparing compounds of the formula (1) and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R1, R3, R4, R6 R11, R13 R14 R15, R16, R17, k, I, and m are as defined herein. The present invention also relates to intermediates represented by the formula (3a) wherin R4, and R5 are independently selected from hydrogen and C1-C6 alkyl; each R13, R14, R15 and R16 is independently selected from hydrogen, C1-C6 alkyl and CH2OH, R17 and R18 are independently C1-C6 alkyl, and k and I are independently an integer from 1 to 3, as well as to a process for preparing these intermediates.

  本发明涉及制备式（1）化合物的方法，以及其药学上可接受的盐、前药和溶剂化物，其中R1、R3、R4、R6、R11、R13、R14、R15、R16、R17、k、I和m的定义如本文所述。本发明还涉及由式（3a）表示的中间体，其中R4和R5分别独立地选择氢和C1-C6烷基；每个R13、R14、R15和R16独立地选择氢、C1-C6烷基和CH2OH，R17和R18分别独立地选择C1-C6烷基，k和I独立地选择1至3之间的整数，以及制备这些中间体的方法。
• Processes for the preparation of substituted bicyclic derivatives
  申请人：Ripin H. B. David

  公开号：US20050026940A1

  公开（公告）日：2005-02-03

  The invention relates to processes for preparing compounds of the formula 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R 1 , R 3 , R 4 , R 6 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , k, l, and m are as defined herein. The compounds of formula 1 are useful intermediates toward preparing compounds that may be used in treating abnormal cell growth in mammals by administering pharmaceutical compositions.

  本发明涉及制备式1化合物的过程，以及其药学上可接受的盐、前药和溶剂化物，其中R1、R3、R4、R6、R11、R13、R14、R15、R16、R17、k、l和m的定义如本文所述。式1化合物是制备可用于治疗哺乳动物异常细胞生长的化合物的有用中间体，通过给药药物组合物。
• CYANOGUANIDINES AND CYANOAMIDINES AS ERBB2 AND EGFR INHIBITORS
  申请人：Wallace Eli

  公开号：US20090012290A1

  公开（公告）日：2009-01-08

  Cyanoguanidine quinazoline and cyanoamidine quinazolamine derivatives that are useful in the treatment of hyperproliferative diseases are disclosed. Methods of treating hyperproliferative diseases in mammals are also disclosed.

  本发明公开了用于治疗增殖性疾病的氰基胍喹嗪和氰基胍喹唑衍生物。还公开了治疗哺乳动物增殖性疾病的方法。
• [EN] CYANOGUANIDINES AND CYANOAMIDINES AS ERBB2 AND EGFR INHIBITORS<br/>[FR] CYANOGUANIDINES ET CYANOAMIDINES UTILISEES COMME INHIBITEURS DE ERBB2 ET EGFR
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2004046101A3

  公开（公告）日：2004-09-16