1-Cyclobutyl-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole synthesis

Yield: 5.21%

Reaction Conditions:

Stage #1:pyrazole-4-boronic acid pinacol ester with sodium hydride in N,N-dimethyl-formamide;mineral oil at 0 - 20; for 0.333333 h;Inert atmosphere;
Stage #2:Bromocyclobutane in N,N-dimethyl-formamide;mineral oil at 20; for 2 h;

Steps:

20A 20A.1-Cyclobutyl-4-(4,4,5,5-tetr m th l-132-di x borolan-2-yl)-1H-pyrazole
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (300 mg, 1.55 mmol) was dissolved in DMF (5 mL) at 0 °C under Ar. NaH (60% in oil, 40.8 mg, 1.70 mmol) was added portionwise, and the reaction mixture was then stirred for 20 minutes at rt. A solution of bromocyclobutane (209 mg, 1.55 mmol) in 1 mL of DMF was added, and stirring was continued 2 h at rt. The reaction mixture was quenched with saturated aq. NH4Cl, and then extracted 3x with EtOAc, washed with brine, dried with Na2SO4, filtered and concentrated. The product was purified by silica gel chromatography to provide pyrazole boronate 20A (40 mg, 5.21 %) . MS (ESI): m/z 249.0 (M+H).

References:

BRISTOL-MYERS SQUIBB COMPANY;SMALLHEER, Joanne M.;HU, Carol Hui;VALENTE, Meriah Neissel;SHAW, Scott A.;VOKITS, Benjamin P.;HALPERN, Oz Scott WO2017/160632, 2017, A1 Location in patent:Page/Page column 96