[Synthesis]
5-Fluoroindole (1.0 g, 7.40 mmol) was dissolved in 1 mL of acetic acid, and the solution was slowly added dropwise to a mixture of dimethylamine (567 mg, 1.42 mL, 12.58 mmol, 40% aqueous solution) and formaldehyde (333 mg, 0.9 mL, 11.09 mmol, 37% aqueous solution) that had been pre-cooled to 0°C. The reaction was carried out under argon protection . The reaction mixture was stirred without cooling for 3 hours. Upon completion of the reaction, the mixture was poured into 20 mL of ice water and the pH was adjusted with base to 11. Subsequently, the organic products in the aqueous phase were extracted with ether, the organic phases were combined and dried with anhydrous magnesium sulfate. After removal of the solvent by evaporation under reduced pressure, the crude product was purified by silica gel column chromatography with chloroform/methanol/ammonia as eluent (90:10:1 to 40:10:1 gradient elution) to afford the target compound 1-(5-fluoro-1H-indol-3-yl)-N,N-dimethylmethylmethaneamine (1.33 g, 6.92 mmol, 93% yield) as a beige solid. The structure of the product was confirmed by 1H NMR and 13C NMR: 1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 7.36-7.31 (m, 1H), 7.25-7.20 (m, 1H), 7.12 (d, J = 2.6 Hz, 1H), 6.95-6.88 (m, 1H), 3.58 (s, 2H), 2.28 (s, 6H), 3.58 (s, 2H), 3.58 (s, 2H), 3.58 (s, 2H) 2.28 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 157.5 (d, J = 234.4 Hz), 132.4, 128.0 (d, J = 9.9 Hz), 125.1, 113.2 (d, J = 4.9 Hz), 111.3 (d, J = 9.7 Hz), 110.0 (d, J = 26.4 Hz ), 103.87 (d, J = 23.5 Hz), 54.1, 44.9. |
[References]
[1] Journal of Biological Chemistry, 2016, vol. 291, # 38, p. 20068 - 20084
[2] Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 9902 - 9913
[3] Journal of the Chemical Society, 1959, p. 1913
[4] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1954, vol. 297, p. 229,233 |