Synthesis
Compound 10b (1.8 g, 14.4 mmol) was dissolved in tetrahydrofuran (30 mL) under nitrogen protection and cooled to -78 °C. 2.5 M n-butyllithium (n-BuLi) solution (6.3 mL, 15.8 mmol) was slowly added dropwise and the reaction mixture was stirred at this temperature for 1 hour. Subsequently, N,N-dimethylformamide (DMF) (1.6 g, 21.6 mmol) was added and the mixture was gradually warmed to room temperature and stirring was continued for 3 hours. After completion of the reaction, the reaction was quenched with saturated ammonium chloride (NH4Cl) solution and extracted with ethyl acetate (EtOAc). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure. Finally, the crude product was purified by silica gel (SiO2) column chromatography with the eluent being a solvent mixture of petroleum ether and ethyl acetate (the ratio was varied from 50:1 to 20:1 gradient) to give the target compound 10c (1.5 g, 49% yield).
References
[1] Patent: WO2014/110705, 2014, A1. Location in patent: Page/Page column 70
[2] Patent: WO2014/110687, 2014, A1. Location in patent: Page/Page column 51
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 1, p. 290 - 306
