Study On The Synthesis Process Of Belinostat

The pathogenesis and the current treatment progress of peripheral T-cell lymphoma(PTCL)have been outlined in the paper and the pharmacological mechanisms,pharmacokinetics,clinical research and synthetic research overview of Belinostat for the treatment of peripheral T-cell lymphoma have also been introduced.The reasonable synthetic route of Belinostat have been choosed in the paper after the theoretical analysis and practical attempt.Two synthetic methods of the route were innovated and the conditions of the synthetic route was examined in detail and the reasonable preparation method of Belinostat was determined at last.In the route,sodium 3-sulfobenzoate was the raw material and sodium 3-carbomethoxybenzenesulfonate(2)was obtained through the esterification reaction with MeOH,then the compound(2)was chlorinated with phosphorous oxychloride to give 3-(methoxycarbonyl)benzenesulfonyl chloride(3),then the compound(3)was reacted with aniline to give the 3-(methoxycarbonyl)benzenesulfonanilide(4),then compound(4)was reducded with the red aluminum reagent to give 3-(Hydroxymethyl)-N-phenylbenzene-sulfonamide(5),and the compound(5)was oxidized with PCC reagent which was loaded on silica gel to obtain 3-formyl-N-phenylbenzenesulfonamide(6),then the compound(6)was subjected to Perkin reaction with acetic anhydride under weak base catalyst to give(2E)-3-[3-(anilinesulfonyl)phenyl]-2-propenoic acid(7),and the compound(7)was chlorinated with oxalyl chloride to give(2E)-3-[3-(anilinesulfonyl)phenyl]-2-acryloyl chloride(8),then the compound(8)was not further processing and directly reacted with hydroxylamine hydrochloride to produce the title compound Belinostat(1)and the total yield was 21.2%.The structure of the target compound was confirmed by 1H-NMR and MS.In the process of preparing Belinostat,many useful process were explored and optimized and the cost was reduced,yield was improved,handling was easier,and it was more suitable for industrial production.The amelioration and Innovation of this paper were described as follows:1.The optimized synthetic route of Belinostat colligated the advantages and disadvantages of the reported routes,materials was obtained more easily,procedures was more simplified and the cost was lower.The total yield was 21.2%,which was significantly higher than which was reported in the literature.2.We chose Red-Al reduction reagent instead of potassium borohydride and lithium chloride reduction system to reduce compound(4),and the reaction time was shorter and procedures was simple.3.We prepared the key intermediate of Belinostat by Perkin reaction and avoided the use of trimethyl phosphonoacetate which was an expensive reagent.The acetic anhydride reagent which was used in this method was cheap and easy to obtain,and it was acted as a solvent in the reaction and could be recycled after the reaction and the method was low cost.