3-（二甲氨基）-1-（3-吡啶基）-2-丙烯-1-酮 | 75415-01-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-（二甲氨基）-1-（3-吡啶基）-2-丙烯-1-酮
• 英文名称: 3-(dimethylamino)-1-(3-pyridinyl)-2-propen-1-one
• 英文别名: N,N-dimethyl-3-oxo-3-(3-pyridinyl)-prop-1-enamine；(Z)-3-(Dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one；(Z)-3-(dimethylamino)-1-pyridin-3-ylprop-2-en-1-one
• CAS: 75415-01-9
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: MZLRFUCMBQWLNV-ALCCZGGFSA-N

物化性质

• 沸点：
  281.4±36.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-（二甲氨基）-1-（3-吡啶基）-2-丙烯-1-酮 在 氢溴酸 、 potassium carbonate 作用下， 以 乙二醇甲醚 为溶剂， 反应 32.0h， 生成 4-<<4-(3-pyridinyl)-2-pyrimidinyl>amino>phenol
  参考文献：
  名称：

  Preparation of substituted N-phenyl-4-aryl-2-pyrimidinamines as mediator release inhibitors

  摘要：

  The role of immunologically released mediators, such as histamine, leukotrienes, and platelet-activating factor, is well-established for asthma and other allergic disorders. Developing therapeutic agents which would block mediator release from mast cells and other relevant cell types would provide a rational approach to asthma therapy. Using human basophil as a screen, a series of 4-aryl-2-(phenylamino)pyrimidines was found which inhibited mediator release. These compounds were prepared by condensing acetyl heterocycles with dimethylformamide dimethyl acetal to form enaminones which are cyclized with aryl guanidines to give pyrimidines. After examining a large number of analogs, N-[3-(1H-imidazol-1-yl)phenyl]-4-(2-pyridinyl)-2-pyrimidinamine (1-27) was chosen for toxicological evaluation.

  DOI：

  10.1021/jm00071a002
• 作为产物：
  描述：

  3-乙酰基吡啶 、 N,N-二甲基甲酰胺二甲基缩醛 反应 5.0h， 以98%的产率得到3-（二甲氨基）-1-（3-吡啶基）-2-丙烯-1-酮
  参考文献：
  名称：

  Synthesis and structure–activity relationships of quaternary ammonium cephalosporins with 3-pyrazolylpyridinium derivatives

  摘要：

  Cephalosporins with 3-pyazolylpyridinium at C-3 position, which is supposed to exhibit synergic activity of ceftazidime and cefoselis, were synthesized and their antibacterial activity against Gram-positive and Gram-negative was inspected. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00203-1

文献信息

• NILOTINIB INTERMEDIATES AND PREPARATION THEREOF
  申请人：WANG Yanling

  公开号：US20100016590A1

  公开（公告）日：2010-01-21

  Intermediates of Nilotinib were prepared, including, for example, 3-(trifluoromethyl-5-(4-methyl-1H-imidazole-1-yl)-benzeneamine; 3-(4-(pyridin-3-yl)pyrimidin-2-ylamino) -4-methylbenzoyl halogen dihydrochloride; and N-(3-Bromo-5-trifluoromethylphenyl)-4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzamide. Nilotinib.3HCl and its crystalline forms are also described.

  尼洛替尼的中间体已经制备好，包括例如3-(三氟甲基-5-(4-甲基-1H-咪唑-1-基)-苯胺；3-(4-(吡啶-3-基)嘧啶-2-基氨基)-4-甲基苯甲酰卤代二盐酸盐；以及N-(3-溴-5-三氟甲基苯基)-4-甲基-3-[[4-(3-吡啶基)-2-嘧啶基]氨基]苯甲酰胺。另外还描述了尼洛替尼.3HCl及其结晶形式。
• METHOD FOR PREPARING NILOTINIB
  申请人：ASYMCHEM LABORATORIES (TIANJIN) CO., LTD

  公开号：US20180148430A1

  公开（公告）日：2018-05-31

  A method for preparing nilotinib includes the following steps: performing an aminocarbonylation reaction on a compound A and 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl) aniline to obtain an amination product; and performing deprotection treatment of an R group on the amination product to obtain the nilotinib, wherein the compound A has a structure shown in formula I, and in formula I, an R group is selected from benzyl, —COCF 3 , —CHO or —CO 2 R′, where an R′ group is C 1 ˜C 10 alkyl, C 1 ˜C 3 alkoxy ethyl or C 7 ˜C 19 aralkyl.

  制备尼洛替尼的方法包括以下步骤：对化合物A和3-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯胺进行氨基甲酰化反应，得到氨基化产物；对氨基化产物上的R基进行去保护处理，得到尼洛替尼。其中，化合物A的结构如公式I所示，在公式I中，R基选自苄基、—COCF3、—CHO或—CO2R'，其中R'基为C1~C10烷基、C1~C3烷氧基乙基或C7~C19芳基烷基。
• [EN] METHOD OF PREPARING NILOTINIB<br/>[FR] PROCÉDÉ DE PRÉPARATION DE NILOTINIB<br/>[ZH] 尼洛替尼的制备方法
  申请人：ASYMCHEM LABORATORIES (TIANJIN) CO LTD

  公开号：WO2016187824A1

  公开（公告）日：2016-12-01

  本发明提供了一种尼洛替尼的制备方法。该制备方法包括以下步骤：将化合物A与3-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯胺进行插羰胺化反应，得到胺化产物；以及将胺化产物进行R基脱保护处理，得到尼洛替尼；其中，化合物A具有式Ⅰ所示结构，且式Ⅰ中，R基选自苄基、-COCF3、-CHO或-CO2R'，其中R'基为C1～C10的烷基、C1～C3的烷氧基乙基或C7～C19的芳烷基。上述制备方法合成路线短，反应条件温和，并且由于采用特殊的原料能够使该制备方法在提高尼洛替尼产率的同时降低工艺成本。
• METHOD OF PREPARING NILOTINIB
  申请人：Asymchem Laboratories (Tianjin) Co., Ltd.

  公开号：EP3305777A1

  公开（公告）日：2018-04-11

  The disclosure provides a method for preparing nilotinib. The preparation method includes the following steps: performing an aminocarbonylation reaction on a compound A and 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl) aniline to obtain an amination product; and performing deprotection treatment of an R group on the amination product to obtain the nilotinib, wherein the compound A has a structure shown in formula I, and in formula I, an R group is selected from benzyl, -COCF3, -CHO or -CO2R', where an R' group is C1∼C10 alkyl, C1∼C3 alkoxy ethyl or C7∼C19 aralkyl. The preparation method is short in synthesis route and mild in reaction condition. Moreover, with adoption of a special raw material, the preparation method may improve a yield of the nilotinib and simultaneously reduce process cost.

  本公开提供了一种尼洛替尼的制备方法。该制备方法包括以下步骤：对化合物 A 和 3-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯胺进行氨基化反应，得到氨基化产物；对胺化产物上的R基进行脱保护处理，得到尼罗替尼，其中化合物A的结构如式I所示，式I中R基选自苄基、-COCF3、-CHO或-CO2R'，其中R'基为C1∼C10烷基、C1∼C3烷氧基乙基或C7∼C19芳烷基。该制备方法合成路线短，反应条件温和。此外，该制备方法采用特殊原料，可提高尼洛替尼的收率，同时降低工艺成本。
• Method for preparing nilotinib
  申请人：ASYMCHEM LABORATORIES (TIANJIN) CO., LTD

  公开号：US10000470B1

  公开（公告）日：2018-06-19

  A method for preparing nilotinib includes the following steps: performing an aminocarbonylation reaction on a compound A and 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl) aniline to obtain an amination product; and performing deprotection treatment of an R group on the amination product to obtain the nilotinib, wherein the compound A has a structure shown in formula I, and in formula I, an R group is selected from benzyl, —COCF3, —CHO or —CO2R′, where an R′ group is C1˜C10 alkyl, C1˜C3 alkoxy ethyl or C7˜C19 aralkyl.

  一种制备尼罗替尼的方法包括以下步骤：对化合物 A 和 3-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯胺进行氨基化反应，得到氨基化产物；对胺化产物上的R基团进行脱保护处理，得到尼罗替尼，其中化合物A具有式I所示的结构，在式I中，R基团选自苄基、-COCF3、-CHO或-CO2R′，其中R′基团为C1˜C10烷基、C1˜C3烷氧基乙基或C7˜C19芳烷基。