5-Amino-2-bromo-4,6-dimethylpyridine synthesis

Yield:897733-12-9 75.3%

Reaction Conditions:

with bromine in dichloromethane at 0 - 25; for 12 h;

Steps:

42.1 Step 1

To a mixture of 2,4-dimethylpyridin-3-amine (25.0 g, 204.64 mmol, 1 eq) in DCM (500 mL) was added a solution of Br2 (163 g, 1.02 mol, 52.75 mL, 5 eq in DCM (300 mL) dropwise at 0 °C, the mixture was stirred at 25 °C for 12 hours. To the mixture was added aq. Na2SC>3 (300mL) and the mixture was stirred at 25 °C for 1 h. Then the mixture was adjusted to pH= 7 by addition of NaHCO₃ slowly. The mixture was extracted with DCM ( 300 mL x 3). The combine organic phase was washed with brine (50 mL), dried with Na₂SO₄ , filtered and concentrated in vacuum. The residue was purified by column chromatography (SiCL, Petroleum ether : Ethyl acetate=l:l) to afford 6-bromo-2,4-dimethyl-pyridin-3-amine (62.0 g, 308 mmol, 75.3% yield, 100% purity) as a yellow oil. ¹H NMR (400 MHz, CDCL) 5 = 7.02 (s, 1H), 3.45 (d, 7 = 16.4 Hz, 2H), 2.37 (s, 3H), 2.13 (s, 3H).

References:

WO2022/133037,2022,A1 Location in patent:Paragraph 0796