Citation: Tian Yawei, Zhou Gang, Zhao Xiaoming, Dan Wenyan. Selective Fluorination of 2-Aminopyrazine Derivatives in Aqueous Phase[J]. Acta Chimica Sinica, ;2018, 76(12): 962-966. doi: 10.6023/A18070307 shu

Selective Fluorination of 2-Aminopyrazine Derivatives in Aqueous Phase

Tongji University, School of Chemical Science & Engineering, Shanghai 200092

Corresponding author: Zhao Xiaoming, xmzhao08@mail.tongji.edu.cn
Received Date: 30 July 2018
Available Online: 8 December 2018
Fund Project: Project supported by the National Natural Science Foundation of China (No. 21272175) and the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities the National Natural Science Foundation of China 21272175

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2-Aminopyrazines are widely found in naturally occurring compounds, drugs and biologically active ingredients. Especially, the compounds containing a fluorinated aminopyrazine have been applied in the pharmaceutical industry. The introduction of a fluorine atom into organic compounds generally leads to a significant change in the chemical, physical and biological properties. Therefore, new method for introducing a fluorine atom into the aminopyrazine ring is highly desirable. Traditional Balz-Schiemann reaction is difficult to employ in the preparation of fluorinated aminopyrazines because of the decomposition of pyrazine derivatives under strong acidic conditions. In general, pyrazines can take place nucleophilic fluorination; aminopyrazines, which is activated by an amino group, can occur electronphilic halogenation; the radical fluorination of pyrazine derivatives has not reported yet. We envisage a direct fluorination of 2-aminopyrazines with Selectfluor may proceed under mild conditions. In this paper, the fluorination of 2-aminopyrazine derivatives with Selectfluor in aqueous phase was studied, and a transition-metal free fluorination of 2-aminopyrazine derivatives was developed. The method affords 5-fluoro-2-aminopyrazines in good yield with excellent chemoselectivity and high regioselectivity. The results suggested that the fluorination may undergo a radical process. Using this method, an enzyme inhibitor having a certain inhibitory effect on analog of B-Raf enzyme was synthesized. The synthesis was as follows: 6-phenyl-2-aminopyrazine (1a, 0.2 mmol), selectfluor (2a, 0.1 mmol), toluene:water [V(toluene):V(water)＝1:1, 2 mL] in a reaction tube. The reaction was carried out at room temperature, monitoring by ¹⁹F NMR. After the completion of the reaction, the reaction mixture was cooled, diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated and purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give 5-fluoro-2-aminopyrazines 3 and 3-fluoro-2-aminopyrazines 3'.
- 2-aminopyrazine,
- selectfluor,
- fluorination,
- chemoselectivity,
- regioselectivity
1. [1]
  (a) Vollhardt, P.; Schore, N. Organic Chemistry, Freeman Palgrave Macmillan, New York, 2011. (b) Wang, M.; Zhang, Y.; Wang, T.; Wang, C.; Xue, D.; Xiao, J. Org. Lett. 2016, 18, 1976. (c) Jean, B.; Marc, L.; Guy, Q. J. Heterocycl. Chem. 1980, 17, 257. (d) Gainer, H.; Kokorudz, M.; Langdon, W. K. J. Org. Chem. 1961, 26, 2360. (e) Bourguignon, J.; Lemarchand, M.; Quéquiner, G. J. Heterocycl. Chem. 1980, 17, 257.
2. [2]
  (a) Hart, B. P.; Haile, W. H.; Licato, N. J.; Bolanowska, W. E.; Mcguire, J. J.; Coward, J. K. J. Med. Chem. 1996, 27, 56. (b) Jhulki, I.; Chanani, P. K.; Abdelwahed, S. H.; Begley, T. P. J. Am. Chem. Soc. 2016, 138, 8324.
3. [3]
  (a) Zou, Y.; Zhao, D.; Yan, C.; Ji, Y.; Liu, J.; Xu, J.; Lai, Y.; Tian, J.; Zhang, Y.; Huang, Z. J. Med. Chem. 2018, 61, 1821. (b) Cheng, X. C.; Liu, X. Y.; Xu, W. F.; Guo, X. L.; Ou, Y. Bioorg. Med. Chem. 2007, 15, 3315. (c) Zhao, Y.; Qian, G.; Ye, Y.; Wright, S.; Chen, H.; Shen, Y.; Liu, F.; Du, L. Org. Lett. 2016, 18, 2495. (d) W chter, G. A.; Davis, M. C.; Martin, A. R.; Franzblau, S. G. J. Med. Chem. 1998, 41, 2436. (e) Kalinowski, D. S.; Sharpe, P. C.; Bernhardt, P. V.; Richardson, D. R. J. Med. Chem. 2008, 51, 331.
4. [4]
  (a) Liu, L. W.; Wang, F. Y.; Tian, F.; Peng, L.; Wang, L. X. Org. Process Res. Dev. 2016, 20, 320. (b) Ashley, J. D.; Stefanick, J. F.; Schroeder, V. A.; Suckow, M. A.; Kiziltepe, T.; Bilgicer, B. J. Med. Chem. 2014, 57, 5282. (c) Wang, G.; Wan, J.; Hu, Y.; Wu, X.; Prhavc, M.; Dyatkina, N.; Rajwanshi, V. K.; Smith, D. B.; Jekle, A.; Kinkade, A. J. Med. Chem. 2016, 59, 4611. (d) Asaki, T.; Kuwano, K.; Morrison, K.; Gatfield, J.; Hamamoto, T.; Clozel, M. J. Med. Chem. 2015, 58, 7128. (e) Guillotin, D.; Austin, P.; Begum, R.; Freitas, M. O.; Merve, A.; Brend, T.; Short, S. C.; Marino, S.; Martin, S. A. Clin. Cancer Res. 2016, 23, 2880. (f) Wang, G.; Wan, J.; Hu, Y.; Wu, X.; Prhavc, M.; Dyatkina, N.; Rajwanshi, V. K.; Smith, D. B.; Jekle, A.; Kinkade, A. J. Med. Chem. 2016, 59, 4611.
5. [5]
  (a) Ryan, S. J.; Schimler, S. D.; Bland, D. C.; Sanford, M. S. Org. Lett. 2015, 46, 1866. (b) Schimler, S. D.; Ryan, S. J.; Bland, D. C.; Anderson, J. E.; Sanford, M. S. J. Org. Chem. 2015, 80, 12137. (c) Sun, H.; DiMagno, S. G. Angew. Chem., Int. Ed. 2006, 45, 2720. (d) Kindon, N.; Andrews, G.; Baxter, A.; Cheshire, D.; Hemsley, P.; Johnson, T.; Liu, Y.; McGinnity, D.; McHale, M.; Mete, A.; Reuberson, J.; Roberts, B.; Steele, J.; Teobald, B.; Unitt, J.; Vaughan, D.; Walters, I.; Stocks, M. J. ACS Med. Chem. Lett. 2017, 8, 981.
6. [6]
  Fier, P. S.; Hartwig, J. F. Science 2013, 342, 956. doi: 10.1126/science.1243759
7. [7]
  Selectfluor made from F₂ and 1, 4-diazabicyclo[2.2.2] octane in the presence of CH₂Cl₂ and BF₃ was reported, see: (a) Banks, R. E.; Mohialdin-Khaffaf, S. N.; Lal, G. S.; Sharif, I.; Syvret, R. G. J. Chem. Soc., Chem. Commun. 1992, 23, 595. (b) Review: Nyffeler, P. T.; Durón, S. G.; Burkart, M. D.; Vincent, S. P.; Wong, C. H. Angew. Chem., Int. Ed. 2004, 36, 192. (c) Account: Singh, R. P.; Shreeve, J. M. Acc. Chem. Res. 2004, 37, 31.
8. [8]
  CCDC 1826147 for 3a contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center.
9. [9]
  CCDC 1847836 for 3a' contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center.
10. [10]
  (a) Gahman, T. C.; Lang, H.; Davis, R. L.; Scranton, S. A. WO 2006124874, 2006[Chem. Abstr. 2006, 146, 13164]. (b) Yin, J.; Zhao, M. M.; And, M. A. H.; Mcnamara, J. M. Org. Lett. 2002, 4, 3481.
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