4-(4-甲基-2-硝基-苯基)-吗啉 | 91181-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 4-(4-甲基-2-硝基-苯基)-吗啉
• 英文名称: 2-(morpholin-4-yl)-5-methylnitrobenzene
• 英文别名: 4-(4-methyl-2-nitro-phenyl)morpholine；N-(2-Nitro-4-tolyl)-morpholin；4-(4-Methyl-2-nitrophenyl)morpholine
• CAS: 91181-62-3
• 化学式: C₁₁H₁₄N₂O₃
• mdl: MFCD16630616
• 分子量: 222.244
• InChiKey: GNPBBZVYDKZTSL-UHFFFAOYSA-N

物化性质

• 沸点：
  119-120 °C(Press: 0.2 Torr)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-甲基-2-硝基-苯基)-吗啉 在 1-甲基吡咯烷 、 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 生成 N-(5-methyl-2-(morpholin-4-yl)phenyl)-N'-(4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)urea
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468
• 作为产物：
  描述：

  吗啉 、 4-溴-3-硝基甲苯 反应 3.0h， 生成 4-(4-甲基-2-硝基-苯基)-吗啉
  参考文献：
  名称：

  [EN] DIKETOPIPERAZINE DERIVATIVES AS P2X7 MODULATORS
  [FR] DÉRIVÉS DE DICÉTOPIPÉRAZINE COMME MODULATEURS DE P2X7

  摘要：

  本发明提供了一种式(I)化合物或其药学上可接受的盐：(I)其中：A代表芳基、杂芳基或杂环基团；上述芳基或杂芳基的任何环或环系可选地被1至3个取代基取代，这些取代基可以相同或不同，选自卤素、C1-6烷基、-CF3、-OCF3、氰基、C1-6烷氧基、-NR10R11、-X-芳基、-X-杂芳基和-X-杂环基；R1、R2、R3、R4和R5各自独立地代表氢、氟、氯、-CF3、氰基或C1-6烷基，使得R1、R2、R3、R4和R5中至少有一个不是氢；R6、R7、R8、R9、R10和R11各自独立地代表氢或C1-6烷基；X代表连接子，选自键、-(CH2)n-和-O-(CH2)n-；n代表1至3的整数。这些化合物或盐能够调节P2X7受体功能，并能拮抗ATP在P2X7受体上的效应（“P2X7受体拮抗剂”）。

  公开号：

  WO2010125103A1

文献信息

• Decarboxylative <i>ipso</i> Amination of Activated Benzoic Acids
  作者：Martin Pichette Drapeau、Janet Bahri、Dominik Lichte、Lukas J. Gooßen

  DOI：10.1002/anie.201812068

  日期：2019.1.14

  the ligand and either air or N‐methylmorpholine N‐oxide as the oxidant, electron‐deficient benzoic acids undergo oxidative decarboxylative coupling with unprotected amines. This operationally simple aniline synthesis is widely applicable with respect to the amine and gives good yields, even on multigram scale. The orthogonality of this reaction to other Pd‐catalyzed cross‐couplings allows the concise

  在以1,10-菲咯啉为配体，空气或N-甲基吗啉N-氧化物为氧化剂的双金属Pd / Cu体系存在下，缺电子的苯甲酸与未保护的胺进行氧化脱羧偶联。这种操作简单的苯胺合成方法在胺类方面具有广泛的应用，即使在数克规模上也能提供良好的收率。该反应与其他Pd催化的交叉偶联的正交性允许通过连续的C-C，C-Cl和C-N官能化简洁地合成多取代的芳烃。机理研究表明，是高价钯物种的中间产物。
• CARBOXYLIC ACID, ACYL SULFONAMIDE AND ACYL SULFAMIDE-DERIVATIZED BICYCLIC AZA-HETEROAROMATICS AS SELECTIVE MCL-1 INHIBITORS AND AS DUAL MCL-1/BCL-2 INHIBITORS
  申请人：University of Maryland, Baltimore

  公开号：US20200299285A1

  公开（公告）日：2020-09-24

  Mcl-1 selective inhibitors, Bcl-2 selective inhibitors, and Mcl-1/Bcl-2 dual inhibitors and methods of using the same for the treatment of disease are disclosed.

  揭示了Mcl-1选择性抑制剂、Bcl-2选择性抑制剂以及Mcl-1/Bcl-2双重抑制剂，以及利用它们用于治疗疾病的方法。
• Synthesis of 3,6-Disubstituted-2-nitrotoruenes by Methylation of Aromatic Nitrocompounds with Dimethylsulfonium Methylide
  作者：Masafumi Kitano、Naohito Ohashi

  DOI：10.1080/00397910008087046

  日期：2000.12

  Abstract 3,6-disubstituted-2-nitrotoluenes were obtained in moderate yield by methylation of 2,5-disubstituted nitrobenzenes with dimethylsulfonium methylide in DMSO-THF mixture.

  摘要 2,5-二取代硝基苯与二甲基锍在DMSO-THF混合液中甲基化，以中等收率得到3,6-二取代-2-硝基甲苯。
• 3- (BENZO [D] [1,3] DIOXOL-5-YLMETHYL) -4- (THIO) OXO-2- (THIO) OXO-AZOLIDIN-5-YLIDENE DERIVATIVES AS ANTIBACTERIAL AGENTS
  申请人：Kotnik Miha

  公开号：US20090247516A1

  公开（公告）日：2009-10-01

  The present invention concerns novel azolidine compounds of Formula (I) wherein X denotes S, NH, CH2 or O, Y and W denotes each independently S or O, Q denotes CH or N, n and m are an integer from 0 to 2, and R1 and R2 denote independently from each other hydrogen, optionally substituted aryl, optionally substituted heterocyclyl, or an optionally substituted (C1-10) aliphatic group, R3 denotes hydrogen, lower alkyl, halogen, lower alkoxy, nitro, and R4 and R5 denote independently from each other hydrogen, halogen or alkyl, with the proviso that if one of R1 and R2 is hydrogen then the respective other one of R1 and R2 does not denote substituted or unsubstituted 2-furyland their salts, that are useful as pharmaceutical agents, e.g. as antibacterial agents, and to pharmaceutical compositions comprising such compounds.

  本发明涉及式（I）的新型氮杂环化合物，其中X表示S、NH、CH2或O，Y和W各自独立地表示S或O，Q表示CH或N，n和m是0到2的整数，R1和R2各自独立地表示氢、可选取代芳基、可选取代杂环基或可选取代（C1-10）脂肪基，R3表示氢、低碳烷基、卤素、低碳烷氧基、硝基，R4和R5各自独立地表示氢、卤素或烷基，但如果R1和R2中的一个是氢，则另一个分别不表示取代或未取代的2-呋喃基。该化合物及其盐可用作制药剂，例如作为抗菌剂，并用于包含该化合物的制药组合物。
• 3-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(thio)oxo-2-(thio)oxo-azolidin-5-ylidene derivatives as antibacterial agents
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP1916249A1

  公开（公告）日：2008-04-30

  The present invention concerns novel azolidine compounds of formula wherein X denotes S, NH, CH2 or O, Y and W denotes each independently S or O, Q denotes CH or N, n and m are an integer from 0 to 2, and R1 and R2 denote independently from each other hydrogen, optionally substituted aryl, optionally substituted heterocyclyl, or an optionally substituted (C1-10) aliphatic group, R3 denotes hydrogen, lower alkyl, halogen, lower alkoxy, nitro, and R4 and R5 denote independently from each other hydrogen, halogen or alkyl, with the proviso that if one of R1 and R2 is hydrogen then the respective other one of R1 and R2 does not denote substituted or unsubstituted 2-furyland their salts, that are useful as pharmaceutical agents, e.g. as antibacterial agents, and to pharmaceutical compositions comprising such compounds.

  本发明涉及式如下的新型氮杂环丁烷化合物 其中 X 表示 S、NH、CH2 或 O，Y 和 W 各自独立地表示 S 或 O，Q 表示 CH 或 N，n 和 m 是 0 至 2 的整数，R1 和 R2 各自独立地表示氢、任选取代的芳基、任选取代的杂环基或任选取代的 (C1-10) 脂肪族基团，R3 表示氢、R3表示氢、低级烷基、卤素、低级烷氧基、硝基，R4 和 R5 各自表示氢、卤素或烷基，但如果 R1 和 R2 中的一个是氢，则 R1 和 R2 中的另一个不表示取代或未取代的 2-糠基它们的盐。例如作为抗菌剂，以及包含这些化合物的药物组合物。