Application background and overview of 7-isoquinoline borate pinacol ester
7-Isoquinoline boronic acid pinacol ester is an alcohol ester derivative, which can be used as a pharmaceutical synthesis intermediate.
Application and preparation of 7-isoquinoline borate pinacol ester
Preparation of 7-isoquinolineboronic acid pinacol ester, the reaction equation is as follows:
The specific operation is as follows: Add 20g of 7‑bromoisoquinoline, 27.1g of triisopropyl borate and 200mL of anhydrous tetrahydrofuran into a three-necked flask, stir for 10 minutes under nitrogen protection, and cool down to‑ in a dry ice/acetone bath. 60℃, add n-butyllithium dropwise, and keep the storage temperature below ‑50℃. After the dropwise addition is completed, stir for 2 hours, and raise the temperature to ‑20℃. Add 2N hydrochloric acid dropwise to pH=6, extract with ethyl acetate 3 times (100mL*3), combine several layers and dry with 100g anhydrous sodium sulfate, filter and concentrate to dryness to obtain 18.3g of oily crude product. Add 100mL petroleum ether and 10mL methyl tert-butyl ether to the crude product and beat overnight, then filter to obtain 14.4g 7-isoquinoline borate pinacol ester, yield: 87.4%
Applications of 7-isoquinoline borate pinacol ester
7-Isoquinoline borate pinacol ester can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:
1) Add 15g of 7-isoquinolineboronic acid pinacol ester and 28.9g of potassium fluoride into a three-necked flask, add 100mL of methanol and 50mL of water, stir and react at room temperature overnight, TLC will show that the reaction is complete the next day, reduce the pressure Evaporate the solvent and water to dryness, control the temperature to less than 45°C polycarbonate, spin dry the solid and dissolve the product twice with 300mL acetone, filter out the insoluble inorganic salts, concentrate the filtrate to dryness and beat it with 50mL MTBE, filter pure pyridine to obtain 14.9g Isoquinoline‑7‑boronic acid potassium trifluoride, yield 80.6%.
2) Quinoline-7-boronic acid potassium trifluoride (1.0eq), 5-chloropyrazine-2-carboxylic acid methyl ester (1.0eq), PdCl2(dppf)2 (3%mol) and sodium carbonate (2.0eq) were added to the reaction flask, and mixed solvent (ethylene glycol diMethyl ether/water=5/1), nitrogen replacement, heating and refluxing for 22 hours. Cool down, filter, add 2N hydrochloric acid to adjust pH=7, extract twice with ethyl acetate, dry with anhydrous sodium sulfate, concentrate to dryness to obtain crude product, and purify the crude product with silica gel column to obtain pure product (yield: 74%).
