5-Bromo-1,3-dimethyl-1H-pyrazole synthesis

Yield:-

Reaction Conditions:

in acetonitrile at 0 - 20; for 18 h;Inert atmosphere;

Steps:

5-bromo-13-dimethyl-1H-pyrazole (95)
A 50-mL round-bottom flask was charged with 3-bromo-5-methyl-1H-pyrazole (2.00 g, 12.4 mmol) under inert atmosphere. MeCN (5 mL) was added, and the mixture was cooled to 0 °C. To the stirring mixture at this temperature was added trimethyloxonium tetrafluoroborate (2.71 g, 14.3 mmol). The resultant mixture was held at 0 °C for 3 hrs, then warmed to RT and stirred for an additional 15 hrs. The reaction was quenched by pouring into sat. aq. NaHCO₃ (30 mL). The mixture was extracted with EtOAc (3 x 20 mL), and the combined organic phases were washed with brine (1 x 50 mL), dried over anhydrous Na₂SO₄, filtered, and solvent was removed from the collected filtrate under reduced pressure. The crude residue was subjected to purification by flash chromatography over silica gel (0-20% EtOAc/PE) to afford the title compound 95. MS (ESI): m/z calc’d for C₅H₈BrN₂ [M+H]⁺: 175, found 175.

References:

MERCK SHARP & DOHME CORP.;KEYLOR, Mitchell, H.;ARDOLINO, Michael, J.;CHAU, Ryan, W.;FULLER, Peter, H.;GULATI, Anmol;JOHNSON, Rebecca Elizabeth;KATTAR, Solomon, D.;MARGREY, Kaila, A.;MORRIELLO, Gregori, J.;NEELAMKAVIL, Santhosh, F.;YAN, Xin;YU, Elsie, C.;ZARATE SAEZ, Cayetena Carmela WO2021/80929, 2021, A1 Location in patent:Page/Page column 78-79