2-甲基-1,2,3,4-四氢-6-三氟甲基喹喔啉 | 345954-29-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-甲基-1,2,3,4-四氢-6-三氟甲基喹喔啉
• 英文名称: 2-methyl-1,2,3,4-tetrahydro-6-trifluoromethylquinoxaline
• 英文别名: 2-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinoxaline
• CAS: 345954-29-2
• 化学式: C₁₀H₁₁F₃N₂
• 分子量: 216.206
• InChiKey: JAQLAQIFVHRADG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-甲基-1,2,3,4-四氢-6-三氟甲基喹喔啉 在 盐酸 、 selenium(IV) oxide 、 水 、 双氧水 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 6.0h， 生成 6-(三氟甲基)喹喔啉-2-甲醛
  参考文献：
  名称：

  Quinoxaline chemistry. Part 15. 4-[2-Quinoxalylmethylenimino]-benzoylglutamates and -benzoates, 4-[2-quinoxalylmethyl-N-methylamino]-benzoylglutamates as analogues of classical antifolate agents. Synthesis, elucidation of structures and in vitro evaluation of antifolate and anticancer activities

  摘要：

  We report on an extension of our previous discovery of in vitro anticancer activity of trifluoromethylquinoxalines as analogues of classical and non-classical antifolic methotrexate and trimetrexate. In this case a small number of Schiff bases were obtained from the reaction of 2-bromethyl-3-R-6(7)trifluoromethylquinoxaline and ethyl p-aminobenzoylglutamate, ethyl p-aminobenzoate, p-toluidine instead of the expected 4-[2-quinoxalyl]methyl-N-methylanilino derivatives, which in turn formed with N-methylanilino derivatives. The reaction mechanism has been put forward. Structure elucidation of both Schiff bases and N-methylanilino analogues was achieved by a combination of 1H and 13C NMR spectra and hetcor experiments. Compounds 3a, 3b, 3c, 8, 11, 12, 13, Ie were tested in antifolic enzyme assay [Lactobacillus casei (LcTS), Leishmania major (LmTs), human Thymidylate synthase (hTs), human TS, human dihydrofolate reductase (hDHFR)] while compounds 3a, 3b, 3c were tested for anticancer activity. These results seem to indicate that the Schiff bases are somewhat active either as anticancer or as folate inhibitors, while compound Ie was selectively active against hDHFR with an inhibition constant (Ki) of 200 nM with a specificity of about 1000-folds with respect to hTS.

  DOI：

  10.1016/s0014-827x(02)00005-8
• 作为产物：
  描述：

  2-Chloro-3-methyl-7-trifluoromethylquinoxaline 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 15.0 ℃ 、303.97 kPa 条件下， 反应 0.83h， 以85%的产率得到2-甲基-1,2,3,4-四氢-6-三氟甲基喹喔啉
  参考文献：
  名称：

  Quinoxaline chemistry. Part 15. 4-[2-Quinoxalylmethylenimino]-benzoylglutamates and -benzoates, 4-[2-quinoxalylmethyl-N-methylamino]-benzoylglutamates as analogues of classical antifolate agents. Synthesis, elucidation of structures and in vitro evaluation of antifolate and anticancer activities

  摘要：

  We report on an extension of our previous discovery of in vitro anticancer activity of trifluoromethylquinoxalines as analogues of classical and non-classical antifolic methotrexate and trimetrexate. In this case a small number of Schiff bases were obtained from the reaction of 2-bromethyl-3-R-6(7)trifluoromethylquinoxaline and ethyl p-aminobenzoylglutamate, ethyl p-aminobenzoate, p-toluidine instead of the expected 4-[2-quinoxalyl]methyl-N-methylanilino derivatives, which in turn formed with N-methylanilino derivatives. The reaction mechanism has been put forward. Structure elucidation of both Schiff bases and N-methylanilino analogues was achieved by a combination of 1H and 13C NMR spectra and hetcor experiments. Compounds 3a, 3b, 3c, 8, 11, 12, 13, Ie were tested in antifolic enzyme assay [Lactobacillus casei (LcTS), Leishmania major (LmTs), human Thymidylate synthase (hTs), human TS, human dihydrofolate reductase (hDHFR)] while compounds 3a, 3b, 3c were tested for anticancer activity. These results seem to indicate that the Schiff bases are somewhat active either as anticancer or as folate inhibitors, while compound Ie was selectively active against hDHFR with an inhibition constant (Ki) of 200 nM with a specificity of about 1000-folds with respect to hTS.

  DOI：

  10.1016/s0014-827x(02)00005-8

文献信息

• Metal-free tandem cyclization/hydrosilylation to construct tetrahydroquinoxalines
  作者：Yixiao Pan、Changjun Chen、Xin Xu、Haoqiang Zhao、Jiahong Han、Huanrong Li、Lijin Xu、Qinghua Fan、Jianliang Xiao

  DOI：10.1039/c7gc03095a

  日期：——

  B(C₆F₅)₃-Catalyzed tandem cyclization/hydrosilylation for the step-economical construction of 1,2,3,4-tetrahydroquinoxalines from readily available starting materials has been developed.

  B(C6F5)3催化的串联环化/氢硅烷化反应，可从易得的起始物构建1,2,3,4-四氢喹啉。
• A solid-phase traceless synthesis of tetrahydroquinoxalines
  作者：Viktor Krchňák、Jennifer Smith、Josef Vágner

  DOI：10.1016/s0040-4039(01)00197-6

  日期：2001.3

  A solid-phase traceless synthesis of tetrahydroquinoxalines with three combinatorial steps is reported. An aldehyde functionalized polystyrene resin was reductively aminated by amino alcohols, and then the resin bound secondary amines were reacted with o-fluoronitrobenzenes. The hydroxy group was mesylated and the nitro group was reduced by tin(II) chloride to the anilines, which spontaneously cyclized

  据报道具有三个组合步骤的固相无痕合成四氢喹喔啉。将醛官能化的聚苯乙烯树脂用氨基醇还原胺化，然后使与树脂结合的仲胺与邻氟硝基苯反应。羟基被甲磺酸化，硝基被氯化锡（II）还原为苯胺，后者自发环化。将所得四氢喹喔啉的仲苯胺氮进一步用酰氯和异氰酸酯衍生化。从树脂上酸解裂解后，得到具有三个多样性点的四氢喹喔啉。
• Solid-Phase Traceless Synthesis of Selected Nitrogen-Containing Heterocyclic Compounds. The Encore Technique for Directed Sorting of Modular Solid Support
  作者：Viktor Krchňák、Jennifer Smith、Josef Vágner

  DOI：10.1135/cccc20011078

  日期：——

  The acid lability of electron-rich N-benzylanilines has been exploited in a linker for the traceless solid-phase synthesis of benzimidazoles, 2-aminobenzimidazoles, quinoxalinones and tetrahydroquinoxalines. The target compound precursors were assembled on a solid-phase support derivatized with either a benzylamine or a benzhydrylamine linker. Exposure to an acidic reagent caused cleavage of the C(benzyl)-N(aniline) bond, releasing the product with only a hydrogen atom on the descending nitrogen. The Encore technique for directed sorting on SynPhase Lanterns has been developed and applied to combinatorial synthesis of generic drug discovery libraries.

  电子富集的N-苯基苯胺的酸敏感性已被利用在无痕固相合成苯并咪唑，2-氨基苯并咪唑，喹啉酮和四氢喹啉的连接剂中。目标化合物的前体在固相支持物上组装，该支持物经过苯基胺或苯基亚胺连接剂衍生化。暴露于酸性试剂会导致C(苯基)-N(苯胺)键的断裂，释放仅带有一个氢原子的产物。Encore技术用于在SynPhase Lanterns上的定向分选已被开发并应用于通用药物发现库的组合合成。
• Quinoxaline chemistry. Part 15. 4-[2-Quinoxalylmethylenimino]-benzoylglutamates and -benzoates, 4-[2-quinoxalylmethyl-N-methylamino]-benzoylglutamates as analogues of classical antifolate agents. Synthesis, elucidation of structures and in vitro evaluation of antifolate and anticancer activities
  作者：Mario Loriga、Sandra Piras、Giuseppe Paglietti、Maria Paola Costi、Alberto Venturelli

  DOI：10.1016/s0014-827x(02)00005-8

  日期：2003.1

  We report on an extension of our previous discovery of in vitro anticancer activity of trifluoromethylquinoxalines as analogues of classical and non-classical antifolic methotrexate and trimetrexate. In this case a small number of Schiff bases were obtained from the reaction of 2-bromethyl-3-R-6(7)trifluoromethylquinoxaline and ethyl p-aminobenzoylglutamate, ethyl p-aminobenzoate, p-toluidine instead of the expected 4-[2-quinoxalyl]methyl-N-methylanilino derivatives, which in turn formed with N-methylanilino derivatives. The reaction mechanism has been put forward. Structure elucidation of both Schiff bases and N-methylanilino analogues was achieved by a combination of 1H and 13C NMR spectra and hetcor experiments. Compounds 3a, 3b, 3c, 8, 11, 12, 13, Ie were tested in antifolic enzyme assay [Lactobacillus casei (LcTS), Leishmania major (LmTs), human Thymidylate synthase (hTs), human TS, human dihydrofolate reductase (hDHFR)] while compounds 3a, 3b, 3c were tested for anticancer activity. These results seem to indicate that the Schiff bases are somewhat active either as anticancer or as folate inhibitors, while compound Ie was selectively active against hDHFR with an inhibition constant (Ki) of 200 nM with a specificity of about 1000-folds with respect to hTS.