2-Amino-5-bromothiazolo[5,4-b]pyridine

13534-97-9

333-20-0

934266-82-7

Step A: 6-Bromopyridin-3-amine (1A, 20 g, 1.0 eq.) was added batchwise to a solution of potassium thiocyanate (5.0 eq.) in acetic acid (0.4 M) at -5 °C. The reaction mixture was cooled to -15 °C and a solution of bromine (Br2, 1.3 eq.) in acetic acid (9.4 M) was slowly added dropwise through a constant pressure dropping funnel. After the dropwise addition, the reaction system was slowly warmed to room temperature and stirred continuously for 12 hours. Upon completion of the reaction, the precipitate was collected by filtration. To the filtrate, 100 mL of ethyl acetate (EtOAc) and 200 mL of water (H2O) were added, followed by concentration under reduced pressure to remove 200 mL of solvent by rotary evaporator. The residue was placed in an ice bath with stirring for 10 min, precipitated as a solid, filtered, and washed twice with a cold 10% methanol (MeOH) solution in ether (Et2O). The filtrates were combined and concentrated, and the product was crystallized in an ice bath and washed again twice with cold 10% ether solution of methanol to give a second batch of product. After vacuum drying, the brown solid product 1B was obtained in 77% yield. The product could be used for subsequent reactions without further purification. The product was characterized as follows: 1H NMR (400 MHz, DMSO-d6) δ ppm 4.94 (br.s, 1H), 7.44 (d, J = 8.34 Hz, 1H), 7.57 (d, J = 8.34 Hz, 1H), 8.04 (br.s., 1H); ESI-MS: m/z 230.0 (M + H)+.