Synthesis
a) Synthesis of 1-methyl-1H-indole-4-carboxaldehyde: Sodium hydride (171 mg, 60% oil dispersion, 4.27 mmol) was added batchwise to an anhydrous N,N-dimethylformamide (DMF, 6.5 mL) solution of 1H-indole-4-carboxaldehyde (413 mg, 2.85 mmol) under argon protection. The reaction mixture was stirred at room temperature for 40 min. Subsequently, iodomethane (0.36 mL, 5.78 mmol) was slowly added dropwise and the reaction continued to be stirred at room temperature for 12 hours. Upon completion of the reaction, the reaction was quenched by the addition of water (25 mL) and extracted with ethyl acetate (3 x 25 mL). The organic phases were combined, washed sequentially with water (20 mL) and saturated saline (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow oily crude product. Purification by silica gel column chromatography (eluent: dichloromethane) gave 1-methyl-1H-indole-4-carboxaldehyde (452 mg, 99% yield) as yellow oil.1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.58 (d, J = 7.2 Hz, 1H). 7.58 (d, J = 2.8 Hz, 1H), 7.38-7.34 (m, 1H), 7.08 (d, J = 3.2 Hz, 1H), 3.87 (s, 3H).
References
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[2] European Journal of Medicinal Chemistry, 2017, vol. 134, p. 13 - 23
[3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 7, p. 2060 - 2079
[4] Journal of Organometallic Chemistry, 2011, vol. 696, # 5, p. 1072 - 1083
[5] Patent: WO2012/47702, 2012, A1. Location in patent: Page/Page column 32
