Synthesis And Study Of Drug Intermediates Isoquinoline-4(1H)-one

The compounds containing the isoquinolone structure are widely foundin nature with a variety of pharmacological effects. Therefore, an effectivesynthetic method of drug intermediates2,3-dihydro-isoquinoline-4-(1H)-one will have important theoretical significance and practical value. weanalyzed the2,3-dihydro-isoquinoline-4(1H)-one combined with theliterature by the raw materials readily available, easy to operate and greenprinciples to got an operableSynthesis route. The major synopsis and resultswere summarized as the following:1. To create a synthetic route of pharmaceutical intermediates2,3-di-hydro-isoquinolin-4-(1H)-one. The total yield was28%2. In the preparing of sulfonamide, Using pyridine as acid-bindingagent, benzylamine and p-toluenesulfonyl chloride molar ratio of1:1.5andyield of90%,12%higher than the literature3. In the preparing of alkylation, We got rid of anhydrous operation andreplaced sodium hydride with potassium carbonate to improve the securityof the reaction; DMF was recovery apply to reduce pollution as well aslower costs.4. In the preparation of ester hydrolysis reaction, We stirred under reflux for2h at70℃conditions with20%sodium hydroxide solution, Thecompletion of the reaction was treated with acid, dried over anhydrous togive the product, yield up to90%. The method is simple, avoiding thetedious post-processing, and low costs.5. In the preparation of target product, The recyclable catalyst cesiumfluoride Celite activator was used again to reduce the cost of the reactionIn summary, Benzylamine as raw material to obtain the targetcompound by acylation, alkylation, hydrolysis of the ester, acylation,cyclization and sulfonamide hydrolysis. The synthetic route has theadvantages of low cost, mild reaction conditions, easy to operate and green,with the prospect of industrial production.