2-甲基-3-苯基-6-三氟甲基喹喔啉 | 102729-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-甲基-3-苯基-6-三氟甲基喹喔啉
• 中文别名: 喹喔啉,2-甲基-3-苯基-6-(三氟甲基)-
• 英文名称: 2-methyl-3-phenyl-6-trifluoromethylquinoxaline
• 英文别名: 2-Methyl-3-phenyl-6-(trifluoromethyl)quinoxaline
• CAS: 102729-44-2
• 化学式: C₁₆H₁₁F₃N₂
• 分子量: 288.272
• InChiKey: CUFMUKGYXDWQQB-UHFFFAOYSA-N

物化性质

• 沸点：
  356.4±37.0 °C(Predicted)
• 密度：
  1.280±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-甲基-3-苯基-6-三氟甲基喹喔啉 在 溴 、 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 以47%的产率得到2-(溴甲基)-3-苯基-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
• 作为产物：
  描述：

  1-苯基-1-丙炔 在 ruthenium trichloride 、 碘苯二乙酸 、 糖精 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 2-甲基-3-苯基-6-三氟甲基喹喔啉
  参考文献：
  名称：

  喹喔啉的立体发散不对称氢化

  摘要：

  对映体富集产物的所有立体异构体的立体发散不对称合成，优选使用催化方法，在有机合成和药物发现中具有极大的兴趣和重要性。在此，我们报道了通过Mn催化的双取代喹喔啉前所未有的立体发散AH，提供了具有高水平非对映和对映选择性的顺式和很少获得的反式手性四氢喹喔啉（THQ）。该转变具有良好的官能团兼容性和广泛的适用性。通过对含有手性 THQ 支架的有价值的生物活性分子的甲基化变体进行简洁和立体选择性合成，进一步强调了该方法的合成效用。

  DOI：

  10.1016/j.chempr.2023.05.006

文献信息

• 2-Phenyl-6(7)-R-substituted quinoxalines N-oxides. Synthesis, structure elucidation and antimicrobial activity
  作者：M Loriga、A Nuvole、G Paglietti、G Fadda、S Zanetti

  DOI：10.1016/0223-5234(90)90147-u

  日期：1990.7
• Loriga, Mario; Paglietti, Giuseppe, Journal of Chemical Research, Miniprint, 1986, # 1, p. 277 - 296
  作者：Loriga, Mario、Paglietti, Giuseppe

  DOI：——

  日期：——
• LORIGA, M.;PAGLIETTI, G., J. CHEM. RES. SYNOP., 1986, N 1, 16-17
  作者：LORIGA, M.、PAGLIETTI, G.

  DOI：——

  日期：——
• 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.
• Stereodivergent asymmetric hydrogenation of quinoxalines
  作者：Chenguang Liu、Xufang Liu、Qiang Liu

  DOI：10.1016/j.chempr.2023.05.006

  日期：2023.9

  products, preferably using a catalytic method, is of great interest and importance in both organic synthesis and drug discovery. Herein, we report an unprecedented stereodivergent AH of di-substituted quinoxalines via Mn catalysis, furnishing cis- and rarely accessed trans-chiral tetrahydroquinoxalines (THQs) with high levels of diastereo- and enantioselectivity. This transformation features excellent functional

  对映体富集产物的所有立体异构体的立体发散不对称合成，优选使用催化方法，在有机合成和药物发现中具有极大的兴趣和重要性。在此，我们报道了通过Mn催化的双取代喹喔啉前所未有的立体发散AH，提供了具有高水平非对映和对映选择性的顺式和很少获得的反式手性四氢喹喔啉（THQ）。该转变具有良好的官能团兼容性和广泛的适用性。通过对含有手性 THQ 支架的有价值的生物活性分子的甲基化变体进行简洁和立体选择性合成，进一步强调了该方法的合成效用。