Background and overview of two preparation methods of 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid indol ester
1-(2-Hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid inalcohol ester is a borate ester derivative, which is widely used in organic synthesis. in the formation of carbon-carbon bonds. In the Suzuki coupling, aryl halides and arylborates or vinyl esters or boronic acids are coupled using Pd(PPh3)4.
Two preparation methods for 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid indol ester
Two preparation methods of 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid indol ester reported 1.
Step 1, 1-(4-iodo-1H-pyrazol-1-yl)-2-methylpropan-2-ol
In a 150mL round bottom flask, 4-iodopyrazole (5.0g, 25.7mmol) was dissolved in DMF (50mL), and 1-chloro-2-methyl-2-propanol (3.1g, 28.3mmol) was added ) and K3PO4 (10.9g, 51.4mmol), then heated to 50°C for 10h. After the reaction is completed, add water to dilute, separate the liquids, and extract the aqueous phase with EtOAc. The organic phases were combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered and concentrated, and the residue was purified by silica gel column chromatography (PE:EtOAc( v/v)=3:1), 4.2g of product was obtained, with a yield of 58%. LCMS (ESI): m/z=281(M+H)+.
Step 2, 1-(2-Hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid inoyl ester
Under nitrogen protection, add 1-(4-iodo-1H-lutidinepyrazol-1-yl)-2-methylpropan-2-ol (4.2g, 15.0 mmol), pinacol diboronate (7.6g, 30.0mmol), Pd(dppf)Cl2 (1.1g, 1.5mmol), AcOK (4.4g, 45mmol), DMF (50mL) , the temperature was raised to 100°C for 2 hours. After the reaction was completed, it was filtered, and the filter residue was washed with EtOAc. Add H2O to the filtrate, extract with EtOAc, combine the organic phases, wash with saturated NaCl solution, dry over anhydrous Na2SO4, and filter. After concentration, 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid which alcohol ester was obtained.
Two preparation methods of 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid indol ester report 2,
Add 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (500mg, 2.58mmol) into the microwave tube , 2,2-dimethyloxapropane (0.57mL, 6.44mmol), cesium carbonate (1.25g, 3.84mmol), acetonitrile (10mL). The reaction solution was incubated with transbiphenylboronic acid in a microwave reactor at 130°C for 1 hour. After the reaction is completed, dichloromethane is added and then filtered. After the filtrate was concentrated, 1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid inoyl ester (480 mg, yield 35%) was obtained. MS m/z(ESI):267[M+H]+.
References
[1] [Invented in China] CN201910769708.6 Pyrazole compounds and pharmaceutical compositions and applications thereof
[2] [Chinese invention, Chinese invention authorization] CN201880021768.3 N-(azaaryl)cyclic lactam-1-carboxamide derivative and its preparation method and application
