4,5-dimethoxy-2-iodobenzoyl chloride | 113258-92-7

• 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: 4,5-dimethoxy-2-iodobenzoyl chloride
• 英文别名: 2-iodo-4,5-dimethoxybenzoyl chloride；Benzoyl chloride, 2-iodo-4,5-dimethoxy-
• CAS: 113258-92-7
• 化学式: C₉H₈ClIO₃
• 分子量: 326.518
• InChiKey: MMKOKTKTGNXIKS-UHFFFAOYSA-N

物化性质

• 沸点：
  382.5±42.0 °C(Predicted)
• 密度：
  1.756±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-dimethoxy-2-iodobenzoyl chloride 在 钯 palladium diacetate 、 甲酸 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 GENZ-644282抑制剂
  参考文献：
  名称：

  5-(2-Aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones:  Variation of N-Alkyl Substituents Modulates Sensitivity to Efflux Transporters Associated with Multidrug Resistance

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo [c, h]-[1,6]naphthyridin-6-one (ARC-111) has potent TOP1-targeting activity and pronounced antitumor activity. Several analogues of ARC-111 were synthesized with NH2, N-alkyl, N,N-dialkyl, pyrrolidinyl, piperidinyl, and piperazinyl substituents at the 2-position of the 5-ethyl group. The relative TOP1-targeting activity and cytotoxicity of these structural analogues were assessed in RPMI8402 and P388 tumor cells and their camptothecin-resistant variants CPT-K5 and P388/CPT45, respectively. Potent TOP1-targeting activity was retained within a series of mono N-alkyl analogues that included NHCH2CH3, NHCH(CH3)(2), and NHC(CH3)(3). TOP1-targeting activity was diminished by the presence of a N-benzyl moiety. In a comparison of a series of N-alkyl-N-isopropyl analogues, activity decreased in the order CH3 > CH2CH3 > CH(CH3)(2). Cytotoxicity in RPMI8402 and P388 did correlate with TOP1-targeting activity. Cytotoxic activity was also determined in KB3-1 cells and its variants KB/V-1 and KBH5.0. As KB/V-1 cells overexpress MDR1 and KBH5.0 cells overexpress BCRP, decreased cytotoxicity in these cell lines relative to the parent cell line is indicative of compounds that are substrates for these efflux transporters. In view of their diminished cytotoxicity in KB/V-1 cells, it appears that the likely demethylated metabolites of ARC-111, i.e., where NH2 or NHCH3 replaces the N(CH3)(2) at the 2-position of the 5-ethyl substituent, are substrates for MDR1. In contrast, no significant difference in cytotoxicity among these three cell lines was observed with other N-alkyl analogues, including NHC2H5, NHCH(CH3)(2), NHC(CH3)(3), N(CH3)(2), N(CH2CH3)(2), NCH3(CH(CH)(3))(2)), and either the pyrrolidinyl or the piperidinyl analogues. The 2-(piperazinyl) analogues were associated with diminished cytotoxicity in KB/V-1 cells, suggesting that the second basic amino substituent is associated with their recognition as substrates by MDR1. Comparative studies on the antitumor activity of ARC-111 and its N-demethylated derivatives (the NHCH3 and NH2 analogues) against SJ-BT45 medulloblastoma xenografts in scid mice revealed that the secondary amine metabolite is at least as active as ARC-111 in vivo, although the primary amine derivative was significantly less potent.

  DOI：

  10.1021/jm049447z
• 作为产物：
  描述：

  2-碘-4,5-二甲氧基苯甲醛 在 草酰氯 、 双氧水 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 4,5-dimethoxy-2-iodobenzoyl chloride
  参考文献：
  名称：

  钯催化的串联反应来构建苯并[ C ^ ]菲啶：应用到苯并的全合成[ C ^ ]菲啶生物碱†

  摘要：

  通过钯催化氮杂双环烯烃与邻碘苯甲酸酯的开环偶联，然后串联环化，可实现苯并[ c ]菲啶的简洁高效合成。该策略已成功应用于苯并[ c ]菲啶生物碱的全合成，如血红碱，白屈菜红碱，尼替丁 和阿维辛。

  DOI：

  10.1039/c0ob01208d
• 作为试剂：
  描述：

  4-[[2-(N-benzyl-N-methylamino)ethyl]amino]-6,7-methylenedioxyquinoline 、 4,5-dimethoxy-2-iodobenzoyl chloride 在 4,5-dimethoxy-2-iodobenzoyl chloride 作用下， 以85的产率得到N-(6,7-methylenedioxyquinolin-4-yl)-N-[2-(N-benzyl-N-methylamino)ethyl]-2-iodo-4,5-dimethoxybenzamide
  参考文献：
  名称：

  J. Med. Chem. 2005, 48, 792 - 804

  摘要：

  DOI：

文献信息

• Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[<i>c</i>]pyrrolo[2,3-<i>h</i>][1,6]naphthyridin-5-one (BPN) Series
  作者：Mohamed S. A. Elsayed、Jeffery J. Nielsen、Sungtae Park、Jeongho Park、Qingyang Liu、Chang H. Kim、Yves Pommier、Keli Agama、Philip S. Low、Mark Cushman

  DOI：10.1021/acs.jmedchem.8b00510

  日期：2018.12.13

  The present account describes the discovery and development of a new benzo[c]pyrrolo[2,3-h][1,6]naphthyridin-5-one (BPN) JAK inhibitory chemotype that has produced selective JAK inhibitors. Sequential palladium chemistry was optimized for the rapid access to a focused library of derivatives to explore the structure–activity relationships of the new scaffold. Several compounds from the series displayed

  该文献描述了已经产生选择性JAK抑制剂的新型苯并[ c ]吡咯并[2，3- h ] [1，6]萘啶-5-酮（BPN）JAK抑制化学型的发现和开发。优化了顺序钯化学，可快速访问聚焦的衍生物库，以探索新支架的结构与活性之间的关系。该系列中的几种化合物对JAK家族的四个成员具有不同选择性的低纳摩尔浓度范围。具有氮杂环丁烷酰胺侧链的化合物20a显示出对JAK1激酶相对于JAK2，JAK3和TYK2的最佳选择性，且纳摩尔浓度低（IC 50 = 3.4 nM）。另一方面，BPN 17b和18对JAK家族具有良好的总体活性，并具有优异的kinome选择性特征。许多新的BPN抑制JAK3介导的STAT-5磷酸化，炎性细胞因子的产生以及原代T细胞的增殖。此外，在类风湿性关节炎动物模型中，BPN 17b的体内结果与托法替尼非常相似。
• Palladium-Catalyzed Carbonylative Annulation Reactions Using Aryl Formate as a CO Source: Synthesis of 2-Substituted Indene-1,3(2<i>H</i>)-dione Derivatives
  作者：Ying Zhang、Jing-Lei Chen、Zhen-Bang Chen、Yong-Ming Zhu、Shun-Jun Ji

  DOI：10.1021/acs.joc.5b01758

  日期：2015.11.6

  An efficient synthesis of 2-substituted indene-1,3(2H)-diones from stable and readily available 1-(2-halophenyl)-1,3-diones by employing phenyl formate as a CO source has been developed. The reaction occurred via palladium-catalyzed intramolecular carbonylative annulation using K3PO4 as a base and DMSO as a solvent at 95 °C. In this protocol, the reaction showed a broad substrate scope with good to

  已经开发了通过使用甲酸苯酯作为CO源从稳定且容易获得的1-（2-卤代苯基）-1,3-二酮有效合成2-取代的茚-1,3（2 H）-二酮的方法。该反应通过在95°C下使用K 3 PO 4为碱和DMSO作为溶剂的钯催化的分子内羰基环化反应进行。在该方案中，反应显示出广泛的底物范围，具有良好或优异的产率。
• Palladium-Catalyzed Intramolecular Asymmetric C–H Functionalization/Cyclization Reaction of Metallocenes: An Efficient Approach toward the Synthesis of Planar Chiral Metallocene Compounds
  作者：Ruixian Deng、Yunze Huang、Xinna Ma、Gencheng Li、Rui Zhu、Bin Wang、Yan-Biao Kang、Zhenhua Gu

  DOI：10.1021/ja500699x

  日期：2014.3.26

  synthesis of planar chiral metallocene compounds is reported. The reaction stereoselectively functionalized one of the ortho C-H bonds of Cp rings by intramolecular cyclization to form indenone derivatives in high yields with excellent enantioselectivity. The mild set of reaction conditions allowed a wide variety of chiral metallocene compounds to be synthesized with broad functional group tolerance. The

  报道了钯催化的平面手性茂金属化合物的不对称合成。该反应通过分子内环化对 Cp 环的邻位 CH 键之一进行立体选择性官能化，以高产率形成具有优异对映选择性的茚酮衍生物。温和的反应条件允许合成具有广泛官能团耐受性的多种手性茂金属化合物。还研究了预装手性对另一个 Cp 环的影响。
• Syntheses of quinazolinones from 2-iodobenzamides and enaminones via copper-catalyzed domino reactions
  作者：Teerawat Songsichan、Jaturong Promsuk、Vatcharin Rukachaisirikul、Juthanat Kaeobamrung

  DOI：10.1039/c4ob00400k

  日期：——

  N-Substituted 2-iodobenzamides and enaminones undergo cascade transformations to achieve quinazolinones via a copper-catalyzed Ullmann-type coupling, a Michael addition and a retro-Mannich reaction. A unique stereochemical feature of this domino process was that Z-enaminones reacted without external ligands, whereas E-enaminones required the assistance of ligands.

  N-取代的2-碘苯甲酰胺和烯胺酮通过级联转化实现喹唉酮的合成，这一过程包括铜催化的乌尔曼型偶联反应、迈克尔加成反应和逆曼尼希反应。该多米诺反应的独特立体化学特征在于，Z-烯胺酮无需外部配体即可反应，而E-烯胺酮则需要配体的辅助。
• Diastereoselective Nickel-Catalyzed Carboiodination Generating Six-Membered Nitrogen-Based Heterocycles
  作者：Austin D. Marchese、Louise Kersting、Mark Lautens

  DOI：10.1021/acs.orglett.9b02797

  日期：2019.9.6

  A scalable, diastereoselective nickel-catalyzed carboiodination reaction is reported that avoids metal-based reducing agents. Novel anti-dihydroquinolones and previously unreported tetrahydroquinolines are now readily prepared. The generation of anti-dihydroquinolones is noteworthy, as this selectivity is opposite to that of the Pd variant. Mechanistic insight into the nature of the nickel-catalyzed

  据报道，可扩展的非对映选择性镍催化的碳碘化反应避免了基于金属的还原剂。现在很容易制备新型的抗二氢喹诺酮类药物和以前未报道的四氢喹啉类药物。抗二氢喹诺酮类药物的生成是值得注意的，因为这种选择性与Pd变体的选择性相反。机械上洞察到镍催化的碳碘化反应的性质是通过实验得出的，这表明了催化剂控制的环化和立体保持性还原的消除。