1-[(4-溴呋喃-2-基)甲基]-4-甲基哌嗪 | 846023-61-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-[(4-溴呋喃-2-基)甲基]-4-甲基哌嗪
• 英文名称: 1-[(4-bromo-2-furyl)methyl]-4-methylpiperazine
• 英文别名: 1-[(4-bromo-furan-2-yl)methyl]-4-methylpiperazine；1-((4-bromofuran-2-yl)methyl)-4-methylpiperazine；2-(4-methylpiperazin-1-yl)-methyl-4-bromofuran；1-[(4-bromofuran-2-yl)methyl]-4-methylpiperazine
• CAS: 846023-61-8
• 化学式: C₁₀H₁₅BrN₂O
• 分子量: 259.146
• InChiKey: YBLODWQYHLSYAD-UHFFFAOYSA-N

物化性质

• 沸点：
  292.8±35.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  19.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(4-溴呋喃-2-基)甲基]-4-甲基哌嗪 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 正丁基锂 、 硼酸三异丙酯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 异丙醇 为溶剂， 反应 28.0h， 生成 (2E/Z)-2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-[(4-methoxy-3-{5-[(4-methyl-1-piperazinyl)methyl]-3-furanyl}phenyl)amino]-2-propenamide
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of a Series of 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles

  摘要：

  Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were prepared and it was found that the 3,5-substituted furan analog had increased activity compared to that of the 2,5-substituted furan isomer. Addition of a methoxy group at C-6 decreased the Src inhibitory activity of the C-7 2,5-substituted furan analog but increased the activity of the C-7 3,5-substituted furan isomer. This compound, 10, was a more potent Src inhibitor than 1 in both enzymatic and cell-based assays. The kinase selectivity profile of 10 was similar to that of 1, with 10 also inhibiting the activity of Abl and Lck. When tested in a solid tumor xenograft model, 10 had comparable oral activity to that of 1.

  DOI：

  10.1021/jm061031t
• 作为产物：
  描述：

  2-(4-methylpiperazin-1-yl)-methyl-4,5-dibromofuran 在 溶剂黄146 、 锌 、 氨 作用下， 以 水 为溶剂， 反应 1.0h， 以97%的产率得到1-[(4-溴呋喃-2-基)甲基]-4-甲基哌嗪
  参考文献：
  名称：

  4-(2,4-dichloro-5-methoxyphenyl)amino-6-methoxy-7-{[5-substituted -amino)methyl]-3-furyl}-3-quinolinecarbonitriles as kinase inhibitors

  摘要：

  这项发明涉及具有Formula I结构的化合物，其中R1、R2、R3和R4如本文所述。

  公开号：

  US20060035930A1

文献信息

• Heterobicyclic pyrazole compounds and methods of use
  申请人：Blake F. James

  公开号：US20070238726A1

  公开（公告）日：2007-10-11

  Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  化合物Ia和Ib的结构，以及其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，可用于抑制受体酪氨酸激酶并治疗由此介导的疾病。公开了使用化合物Ia和Ib的结构，以及其立体异构体、几何异构体、互变异构体、溶剂合物和药学上可接受的盐的方法，用于体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病，或相关的病理条件。
• Process for preparation of 4-amino-3-quinolinecarbonitriles
  申请人：Sutherland Wiggins Karen

  公开号：US20050043537A1

  公开（公告）日：2005-02-24

  This invention discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile comprising combining an amine compound with a cyanoacetic acid and an acid catalyst to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline in an alcoholic solvent and a trialkylorthoformate to yield a 3-amino-2-cyanoacrylamide; combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 4-amino-3-quinolinecarbonitrile and also discloses a process for the preparation of a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile comprising combining a disubstituted 3-amino thiophene with a cyanoacetamide and trialkylorthoformate in an alcoholic solvent to obtain a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride and acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile and also discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile by combining an amine compound with a cyanoacetic acid and a peptide coupling reagent to obtain a suspension; filtering the suspension to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline, an alcoholic solvent, and triethylorthoformate to yield a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride to yield a 4-amino-3-quinolinecarbonitrile.

  这项发明揭示了一种制备4-氨基-3-喹啉碳腈的过程，包括将胺化合物与氰乙酸和酸催化剂结合以产生氰乙酰胺；将氰乙酰胺与醇溶剂和三烷基正甲酸酯中的一个或多个取代苯胺缩合以产生3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷在乙腈、丁腈、甲苯或二甲苯中结合，可选地在催化剂存在的情况下以产生4-氨基-3-喹啉碳腈，并且还揭示了一种制备7-氨基噻吩[3,2-b]吡啶-6-碳腈的过程，包括将二取代的3-氨基噻吩与氰乙酰胺和三烷基正甲酸酯在醇溶剂中结合以获得3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷和乙腈、丁腈、甲苯或二甲苯结合，可选地在催化剂存在的情况下以产生7-氨基噻吩[3,2-b]吡啶-6-碳腈，并且还揭示了一种通过将胺化合物与氰乙酸和肽偶联试剂结合以获得悬浮液；过滤悬浮液以产生氰乙酰胺；将氰乙酰胺与一个或多个取代苯胺、醇溶剂和三乙基正甲酸酯缩合以产生3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氯化磷结合以产生4-氨基-3-喹啉碳腈的制备过程。
• C-5 Substituted heteroaryl 3-pyridinecarbonitriles as PKCθ inhibitors: Part I
  作者：Joan Subrath、Daniel Wang、Biqi Wu、Chuansheng Niu、Diane H. Boschelli、Julie Lee、Xiaoke Yang、Agnes Brennan、Divya Chaudhary

  DOI：10.1016/j.bmcl.2009.07.109

  日期：2009.9

  We earlier reported that 3-pyridinecarbonitriiles with a 4-methylindolyl-5-amino group at C-4 and a phenyl group at C-5 were inhibitors of PKCθ. Keeping the group at C-4 of the pyridine core constant, we varied the water solubilizing group on the phenyl ring at C-5 and then replaced the C-5 phenyl ring with several monocyclic heteroaryl rings, including furan, thiophene and pyridine. Analog 6e with

  我们之前报道过，在C-4处带有4-甲基吲哚基-5-氨基和在C-5处带有苯基的3-吡啶碳腈是PKCθ的抑制剂。保持吡啶核的C-4处的基团恒定，我们改变C-5处苯环上的水溶性基团，然后用几个单环杂芳基环（包括呋喃，噻吩和吡啶）取代C-5苯环。在C-4处带有4-甲基吲哚-5-基氨基和C [5-[（4-甲基哌嗪-1-基）甲基] -2-呋喃基的类似物6e的IC 50值为4.5 nM。抑制PKCθ。
• [EN] PROCESS FOR THE PREPARATION OF 4-AMINO-3-QUINOLINECARBONITRILES<br/>[FR] PROCEDE DE PREPARATION DE 4-AMINO-3-QUINOLEINECARBONITRILES
  申请人：WYETH CORP

  公开号：WO2005019201A2

  公开（公告）日：2005-03-03

  This invention discloses a process for the preparation of a 4-amino-3quinolinecarbonitrile comprising combining an amine compound with a cyanoacetic acid and an acid catalyst to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up-to tetra-substituted aniline in an alcoholic solvent and a trialkylorthoformate to yield an 2-amino-2-cyanoacrylamide; combining the 3-amino2-cyanoacrylamide with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 4-amino-3quinolinecarbonitrile and also discloses a process for the preparation of a 7-amino-thieno[3,2-b]pyridine­6-carbonitrile comprising combining a 3-amino thiophene with a cyanoacetamide and trial kylorthoformate in an alcoholic solvent to obtain a 3-amino2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride and acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile and also discloses a process for the preparation of a 4 amino-3-quinolinecarbonitrile comprising: combining an amine compound with cyanoacetic acid and a peptide coupling reagent to obtain a suspension; filtering the suspension; to yield cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline with an alcoholic solvent to yield a 4-amino-3-quinolinecarbonitrile, and the invention discloses a process for obtaining a cyanoacetamide.

  本发明公开了一种制备4-氨基-3-喹啉羧腈的方法，包括将胺化合物与氰乙酸和酸催化剂结合以得到氰乙酰胺；将氰乙酰胺与可选的高达四取代苯胺在醇溶剂和三烷基正酸酐中缩合，以得到2-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氧化磷酰氯在乙腈、丁腈、甲苯或二甲苯中结合，可选地在催化剂的存在下，以得到4-氨基-3-喹啉羧腈。本发明还公开了一种制备7-氨基噻吩[3,2-b]吡啶-6-羧腈的方法，包括将3-氨基噻吩与氰乙酰胺和三烷基正酸酐在醇溶剂中结合以得到3-氨基-2-氰基丙烯酰胺；将3-氨基-2-氰基丙烯酰胺与氧化磷酰氯和乙腈、丁腈、甲苯或二甲苯结合，可选地在催化剂的存在下，以得到7-氨基噻吩[3,2-b]吡啶-6-羧腈。本发明还公开了一种制备4-氨基-3-喹啉羧腈的方法，包括将胺化合物与氰乙酸和肽偶联试剂结合以得到悬浮液；过滤悬浮液以得到氰乙酰胺；将氰乙酰胺与可选的高达四取代苯胺在醇溶剂中缩合，以得到4-氨基-3-喹啉羧腈。本发明还公开了一种获得氰乙酰胺的方法。
• HETEROBICYCLIC PYRAZOLE COMPOUNDS AND METHODS OF USE
  申请人：Blake James F.

  公开号：US20100256356A1

  公开（公告）日：2010-10-07

  Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式Ia和Ib的化合物及其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，可用于抑制受体酪氨酸激酶并治疗由此介导的疾病。本文揭示了使用公式Ia和Ib的化合物及其立体异构体、几何异构体、互变异构体、溶剂合物和药学上可接受的盐的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗此类疾病或相关病理条件。