Step 64a: Synthesis of 5-bromo-N,N-dimethylpyridin-2-amine (Compound 0601-114)
To a solution of 5-bromopyridin-2-amine (1.0 g, 5.8 mmol) in tetrahydrofuran (THF, 25 mL) was added sodium hydride (NaH, 60% dispersed in mineral oil, 0.92 g, 23.1 mmol) at 0°C and the reaction mixture was stirred for 10 minutes. Subsequently, iodomethane (CH3I, 1 mL, 16 mmol) was added and the reaction continued to be stirred for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of water (30 mL) and extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate, 10% v/v) to give the title compound (1.1 g, 94% yield) as a white solid.
LCMS: 203 [M+2]+.
1H NMR (400 MHz, DMSO-d6) δ 2.99 (s, 6H), 6.61 (d, J = 9.6 Hz, 1H), 7.62 (dd, J = 9.2, 2.8 Hz, 1H), 8.12 (d, J = 2.4 Hz, 1H).