4,5-DibroMo-2-Methyl-2H-1,2,3-triazole synthesis

Yield: 61.2%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 0 - 20;

Steps:

451.1 Step 1 :
To a solution of 4,5-dibromo-1H-1,2,3-triazole (0.401 g, 1.768 mmol) in DMF (6 mL) at 0 °C (in an ice-water bath) was added first potassium carbonate (0.366 g, 2.65 mmol) and then iodomethane (0.116 mL, 1.856 mmol) was added dropwise. After stirring lh, the reaction appears to be incomplete by HPLC. Added additional 50uL iodomethane, continued stirring, now at room temp. Reaction still appears to incomplete. Added additional 50uL iodomethane. Quenched with lOmL water. Extracted 2x 50mL EtOAc. Washed combined EtOac lx 10% LiCl, lx brine. Then dried over sodium suflate, filtered and concentrated. Loaded onto a 40g ISCO column for purification by flash chromatography, eluting with 0-100% EtOAc in hexanes. Two peaks elute, the first eluting being larger by UV absorbance, but giving no MS signal. This is 4,5-dibromo-2-methyl-2H-1,2,3-triazole (0.266 g, 1.082 mmol, 61.2 % yield), designated Isomer 2. HPLC IR 0.90 min (analytical HPLC Method A). NMR (400MHz, chloroform-d) d 4.17 (s, 3H) . The second peak is smaller by UV, but gives the correct mass and dibromo isotopic pattern in MS. This material is 4,5-dibromo-2-methyl-2H-1,2,3-triazole (0.101 g, 1.082 mmol, 61.2 % yield) designated Isomer 1. LCMS m/z 242.0 / 244.0 (M+H)+; HPLC /R 0.67 min (analytical HPLC Method A). 'H NMR (400MHz, chloroform-d) d 4.08 (s, 3H)

References:

BRISTOL-MYERS SQUIBB COMPANY;SPERGEL, Steven H.;PITTS, William J.;MERTZMAN, Michael E.;MOSLIN, Ryan M.;SHERWOOD, Trevor C.;GILMORE, John L.;DYCKMAN, Alaric J. WO2020/92196, 2020, A1 Location in patent:Page/Page column 208-209