Yield:-

Reaction Conditions:

with hydrogen bromide;dihydrogen peroxide in water at 70; for 2 h;

Steps:

154.1 Step 1: 3-bromo-2-methylpyridin-4-amine
A solution of 2-methylpyridin-4-amine (3.00 g, 27.7 mmol, 1.00 eq) in 40.0% HBr (30.0 rnL) aqueous solution was stirred at 70 °C and a solution of H2O2 (12.6 g, 55.5 mmol, 10.7 mL, 15.0% purity, 2.00 eq) was added dropwise over 1 hr period at such a rate that the temperature of the reaction mixture remained at 70 °C. The mixture was stirred for another J h at 70 °C. The mixture was poured on to crushed ice (40.0 g). The pH was adjusted to 7 with solid NaHCCb. The mixture was extracted with EtOAc (50.0 mL * 3). The combined organic layers were dried over Na2SC>4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (S1O2, Petroleum ether/Ethyl acetate = 1/0 to 0/1). 3-Bromo- 2-methylpyridin-4~amine (3 00 g, crude) was obtained as a yellow solid. 1 H NMR CD30D 400 MHz d = ppm 7.76 (d, J=5.8 Hz, 1H), 6.52 (d, J=5.8 Hz, IH), 2.48 (s, 3H).

References:

FULCRUM THERAPEUTICS, INC.;EFREMOV, Ivan Viktorovich;KAZMIRSKI, Steven;LI, Qingyi;THOMPSON, III, Lorin A.;WALLACE, Owen Brendan;JOHNSTONE, Shawn Donald;ZHOU, Feng;RAHL, Peter WO2020/190754, 2020, A1 Location in patent:Paragraph 1246