Preparation background and overview of 7-azaindole-5-boronic acid pinacol ester
7-Azaindole-5-boronic acid pinacol ester belongs to nitrogen-containing heterocyclic boronic acid esters. Nitrogen-containing heterocyclic boric acid and its esters can be used for the synthesis and design of a series of new drugs and high-throughput screening of compound libraries. Established, it is widely used in the fields of medicine, pesticide intermediates, biologically active preparations or materials research, and occupies an extremely important position as nitrate tetrafluoroborate. Especially in biomedicine, heterocyclic boronic acid compounds can not only be used as enzyme inhibitors for the treatment of tumors, microbial infections and other diseases, but can also be used as fluorescent probes to identify hydrogen peroxide, sugars, copper ions, and fluoride ions. and fluorescent probes for substances such as catecholamines.
Preparation of 7-azaindole-5-boronic acid pinacol ester
A synthesis process for heterocyclic boronic acid compounds, including the following steps:
Step 1: Add triethylamine (0.20mol) to a dichloromethane (50ml) solution containing 5-chloro-7-azaindole (3g, 0.02mol) at 0-5°C, and then stir A solution of dichloromethane (100ml) containing mica tert-butyldimethylsilyl chloride (0.2mol) was added dropwise, and then the reaction was stirred at room temperature overnight until TLC showed that the reaction was complete. After the reaction was complete, 50ml of water and 10ml of 0.1mol/L were added. Dilute hydrochloric acid, layer the dichloromethane phase and wash it with 50ml of water, 50ml of saturated sodium carbonate solution and 50ml of saturated sodium chloride, then evaporate the solvent, wash it with acetone three times and then dry it to obtain a yellow solid;
Step 2: Dissolve the above yellow solid in 50ml THF, add 0.005mol sodium carbonate (0.53g) while keeping the reaction system temperature at -5°C, and then slowly add trimethyl borate (4.6ml, 0.04mol) , after the addition, the temperature was raised to room temperature, and the solvent was evaporated under reduced pressure to obtain a yellow oily object;
Step 3: Add 80ml of ethyl acetate and 0.02mol of pinacol to the above yellow oily object, reflux overnight until TLC shows that the reaction is complete, evaporate the solvent, add 100ml of acetone to the residue, stir and filter, and concentrate the filtrate to After drying, a colorless oily substance is obtained;
Step 4: Add 50 ml of diethyl ether and 30 ml of dilute hydrochloric acid with a concentration of 0.1 mol/L to the above colorless oil, stir overnight, evaporate the solvent, and extract the residue with 30 ml of ethyl acetate. Use anhydrous ethyl acetate phase Dry with sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain a crude product, which is then recrystallized with chloroform-petroleum ether (20 ml) with a volume ratio of 1:1 to obtain a white solid. 2.78 g of white solid is obtained, which is 7-azaindole. -5-Pinacol borate, HPLC purity 99.8%, total yield 56.8%.
1H-NMR (CDCl3, 500MHz) δ: 1.33 (s, 12H), 8.85 (s, 1H), 8.53 (d, 1H), 8.29(d,1H), 7.91(s,1H).
References
[1][China invention, China invention authorization] CN201410664398.9 Synthesis process of heterocyclic boric acid compounds
