Synthesis
GENERAL STEPS: N-(2-chloroethyl)morpholine hydrochloride (1.25 g, 6.70 mmol) was added to a solution of anhydrous N,N-dimethylformamide (20 mL) containing pinacol ester of 4-pyrazoleboronic acid (1.00 g, 5.15 mmol) and cesium carbonate (5.54 g, 17.01 mmol) at 0 °C. After stirring for 30 min, the ice water bath was removed. The reaction mixture was continued to be stirred at room temperature for 4 days. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (150 mL) and washed with brine (3 x 100 mL). The organic layer was dried with anhydrous sodium sulfate and subsequently concentrated under reduced pressure. The crude product was purified by fast column chromatography (Method L7; 12 g silica gel; eluent: ethyl acetate) to afford 1-(2-morpholinylethyl)-1H-pyrazole-4-boronic acid pinacol ester 0.75 g (2.44 mmol, 47% yield). analysis by GC-MS (Method L9) showed R1 = 5.49 min; (no mass detected).1H NMR ( 300 MHz, chloroform-d, method M2) δ 7.80-7.75 (m, 1H), 7.73 (s, 1H), 4.25 (t, J = 6.8 Hz, 2H), 3.73-3.44 (m, 4H), 2.81 (t, J = 6.8 Hz, 2H), 2.50-2.42 (m, 4H), 1.32 (s, 12H).
References
[1] Patent: WO2017/178416, 2017, A1. Location in patent: Page/Page column 116
[2] Patent: WO2010/75270, 2010, A1. Location in patent: Page/Page column 160
