Synthesis
General procedure for the synthesis of 6-bromo-2-methyl-3,4-dihydro-2H-isoquinolin-1(2H)-one from 6-bromo-3,4-dihydro-2H-isoquinolin-1-one and iodomethane: 6-bromo-3,4-dihydro-2H-isoquinolin-1-one (500 mg, 2.2 mmol) was dissolved in DMF (3 mL) and the solution was cooled down to 0 °C. Under argon protection, 60% NaH (121 mg, 3.0 mmol) was added and the reaction mixture was stirred for 20 min. Subsequently, methyl iodide (0.275 mL, 4.4 mmol) was added and stirring was continued at 0 °C for 1 hour. Upon completion of the reaction, ice water was added to the mixture and the precipitate was collected by filtration. The resulting solid was dried in a vacuum oven at 50 °C for 12 h to afford the target product 6-bromo-2-methyl-3,4-dihydroisoquinolin-1(2H)-one in 73% yield. Spectral analysis of the product showed m/z 240/242 [M + H]+ with a retention time (rt) of 0.89 min (LC-MS method V012_S01).
References
[1] Patent: WO2014/140075, 2014, A1. Location in patent: Page/Page column 209-210
[2] Patent: US2014/275025, 2014, A1. Location in patent: Paragraph 0537; 0538
[3] Patent: US2016/251376, 2016, A1. Location in patent: Paragraph 0852; 0855; 0856
[4] Patent: US2018/51013, 2018, A1. Location in patent: Paragraph 0597; 0599
