6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridine | 183433-64-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridine
• 英文别名: 2-Chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-6-methoxypyridine
• CAS: 183433-64-9
• 化学式: C₁₁H₁₄ClNO₃
• 分子量: 243.69
• InChiKey: LBSOLHHYSZTSSJ-UHFFFAOYSA-N

物化性质

• 沸点：
  344.2±42.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridine 在 palladium on activated charcoal palladium diacetate 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 sodium tetrahydroborate 、 四氧化锇 、 正丁基锂 、 三甲基氯硅烷 、 4-acetoxy-2,2,6,6-tetramethylpiperidine-1-oxyl 、 十二/十四烷基二甲基氧化胺 、 PS-30 catalyst 、 巴拉松 、 potassium tert-butylate 、 四丁基氯化铵 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 sodium iodide 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 三氟乙酸 、 叔丁醇 为溶剂， -30.0~110.0 ℃ 、103.42 kPa 条件下， 反应 254.67h， 生成 7-乙基-10-羟基喜树碱
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f
• 作为产物：
  描述：

  柠嗪酸 在 三甲基氯硅烷 、 POPCl₃ 、 四甲基氯化铵 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 35.0h， 生成 6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridine
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f

文献信息

• Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents
  作者：Feijie Xu、Wenlong Li、Wen Shuai、Limei Yang、Yi Bi、Cong Ma、Hequan Yao、Shengtao Xu、Zheying Zhu、Jinyi Xu

  DOI：10.1016/j.ejmech.2019.04.008

  日期：2019.7

  derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC50 values ranging from 0.023 to 0.045 μM against a panel of cancer cell lines. Further mechanism study results demonstrated that compound 16f effectively inhibited the microtubule polymerization by binding

  通过引入吡啶环进一步优化母体查尔酮化合物（2a）的三甲氧基苯基骨架，提供了一系列新型的吡啶-查尔酮衍生物作为潜在的抗微管蛋白剂。评价所有目标化合物的抗增殖活性。其中，代表性的化合物16F显示出与IC的最有效的活性50值范围从0.023至0.045  μ中号针对癌细胞系的面板。进一步的机理研究结果表明，化合物16f通过与微管蛋白的秋水仙碱位点结合，有效抑制了微管聚合。此外，细胞机制研究显示16f导致G2 / M期停滞，诱导细胞凋亡并破坏细胞内微管网络。同样，16f减少了细胞迁移并破坏了人脐静脉内皮细胞（HUVEC）的毛细血管样形成。重要的是，16f在H22异种移植模型中显着抑制了肿瘤的生长，而没有明显的毒性，它比参考化合物CA-4强，这表明值得研究16f作为有效的微管去稳定剂用于癌症治疗。
• Synthesis of (+/-) mappicine and mappicine ketone
  作者：Kevin E. Henegar、Ted A. Baughman

  DOI：10.1002/jhet.5570400407

  日期：2003.7

  Mappicine and mappicine ketone are camptothecin analogs of interest as antiviral agents. A novel synthesis of these compounds is described using a Friedlander condensation. The requisite ketone is prepared via a regioselective ortho-directed metallation/alkylation of a trisubstituted pyridine. This is condensed with N-t-butyloxycarbonyl-o-aminobenzaldehyde as a convenient, stable o-aminobenzaldehyde

  Mappicine和Mappicine酮是喜树碱类似物的抗病毒剂。使用Friedlander缩合描述了这些化合物的新合成方法。必要的酮是通过三取代吡啶的区域选择性邻位定向金属化/烷基化制备的。将其与Nt-丁氧基羰基-邻氨基苯甲醛缩合，作为弗里德兰德缩合反应中方便，稳定的邻氨基苯甲醛当量。
• Practical Asymmetric Synthesis of (<i>S</i>)-4-Ethyl-7,8-dihydro-4-hydroxy-1<i>H</i>-pyrano[3,4-f]indolizine- 3,6,10(4<i>H</i>)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs
  作者：Kevin E. Henegar、Scott W. Ashford、Ted A. Baughman、John C. Sih、Rui-Lin Gu

  DOI：10.1021/jo970173f

  日期：1997.9.1

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.