N-(2-(tert-butoxycarbonylamino)phenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide | 1030927-09-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-(tert-butoxycarbonylamino)phenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide
• 英文别名: n-(2-t-butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide；N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide；tert-butyl N-[2-[[4-(3-cyano-5-formylpyridin-2-yl)benzoyl]amino]phenyl]carbamate
• CAS: 1030927-09-3
• 化学式: C₂₅H₂₂N₄O₄
• 分子量: 442.474
• InChiKey: SGWGLJCXIPYCAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-(tert-butoxycarbonylamino)phenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide 在 氯甲酸乙酯 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 tert-butyl {2-[(4-{3-cyano-5-[(ethylamino)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate
  参考文献：
  名称：

  Flexible and Scalable Route to HDAc Inhibitors Containing an Unusual Trisubstituted Pyridine Core

  摘要：

  A scalable route to histone deacetylase inhibitors containing an unusual 2-aryl-3-cyano-5-aminomethylpyridine core has been developed which has the flexibility to deliver a range of compounds on at least a multigram scale. The key step involves a novel Mannich reaction using 3-dimethylaminoacrolein, formaldehyde, and a secondary amine to yield a 2-(alkylaminomethyl)-3-dimethylaminoacrolein. Tuning of this reaction in process development was fundamental to the success of the approach in terms of flexibility and operability on scale-up. This new methodology will also enable access an underutilised family of 3,5-disubstituted pyrid-2-ones and 2,3,5-trisubstituted pyridines.

  DOI：

  10.1021/op300021m
• 作为产物：
  描述：

  N-Boc-1,2-亚苯基二胺 在 N-甲基吗啉 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 7.5h， 生成 N-(2-(tert-butoxycarbonylamino)phenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide
  参考文献：
  名称：

  Flexible and Scalable Route to HDAc Inhibitors Containing an Unusual Trisubstituted Pyridine Core

  摘要：

  A scalable route to histone deacetylase inhibitors containing an unusual 2-aryl-3-cyano-5-aminomethylpyridine core has been developed which has the flexibility to deliver a range of compounds on at least a multigram scale. The key step involves a novel Mannich reaction using 3-dimethylaminoacrolein, formaldehyde, and a secondary amine to yield a 2-(alkylaminomethyl)-3-dimethylaminoacrolein. Tuning of this reaction in process development was fundamental to the success of the approach in terms of flexibility and operability on scale-up. This new methodology will also enable access an underutilised family of 3,5-disubstituted pyrid-2-ones and 2,3,5-trisubstituted pyridines.

  DOI：

  10.1021/op300021m

文献信息

• Benzamide Compounds
  申请人：Gibson Keith Hopkinson

  公开号：US20080293687A1

  公开（公告）日：2008-11-27

  The invention concerns benzamide compounds of Formula (I), wherein R 1a , R 1b , R 1c , R 2 , R 3 , R 4 , m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of histone deacetylase (HDAC).

  这项发明涉及公式（I）的苯甲酰胺化合物，其中R1a、R1b、R1c、R2、R3、R4、m和n具有描述中定义的任意含义；它们的制备过程，含有它们的药物组合物以及它们在制造用作抗增殖剂的药物时的用途，用于预防或治疗对组蛋白去乙酰化酶（HDAC）抑制敏感的肿瘤或其他增殖性疾病。
• Benzamide compounds
  申请人：AstraZeneca

  公开号：US07897778B2

  公开（公告）日：2011-03-01

  The invention concerns benzamide compounds of Formula (I), wherein R1a, R1b, R1c, R2, R3, R4, m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of histone deacetylase (HDAC).

  本发明涉及式(I)的苯甲酰胺化合物，其中R1a、R1b、R1c、R2、R3、R4、m和n具有描述中定义的任何含义；它们的制备方法，含有它们的制药组合物以及它们在制造用作组织蛋白去乙酰化酶（HDAC）抑制剂的药物的预防或治疗对肿瘤或其他增生性疾病敏感的增生症状中的使用。
• Design and campaign synthesis of pyridine-based histone deacetylase inhibitors
  作者：David M. Andrews、Keith M. Gibson、Mark A. Graham、Zbigniew S. Matusiak、Craig A. Roberts、Elaine S.E. Stokes、Madeleine C. Brady、Christine M. Chresta

  DOI：10.1016/j.bmcl.2008.03.058

  日期：2008.4

  A lead benzamide, bearing a cyanopyridyl moiety (3), was identified as a potent and low molecular weight histone deacetylase ( HDAC) inhibitor. Various replacements of the cyano group were explored at the C3-position, along with the exploration of solubility-enhancing groups at the C5-position. It was determined that cyano substitution at the C3-position of the pyridyl core, along with a methylazetidinyl substituent at the C5-position yielded optimal HDAC1 inhibition and anti-proliferative activity in HCT-116 cells. (c) 2008 Elsevier Ltd. All rights reserved.
• US7897778B2
  申请人：——

  公开号：US7897778B2

  公开（公告）日：2011-03-01
• [EN] BENZAMIDE COMPOUNDS<br/>[FR] COMPOSES DE BENZAMIDE
  申请人：ASTRAZENECA AB

  公开号：WO2006024841A2

  公开（公告）日：2006-03-09

  The invention concerns benzamide compounds of Formula (I), wherein R1a, R1b, R1c, R2, R3, R4, m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of histone deacetylase (HDAC).