新产品编号:1544541

Chemical Name: (E)-5-[4-[1-(5-Benzyloxy-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ylmethyl)pyrrolidin-2(S)-yl]methoxy]benzylidene]thiazolidine-2,4-dione maleate
项目整合开发状态: Preclinical
项目研究机构: Dr. Reddy's Research Foundation (Originator)
合成路线:The known benzofuran carbinol (I) was converted to mesylate (II) upon treatment with methanesulfonyl chloride and triethylamine and then condensed with (S)-prolinol (III) at 120 C to afford adduct (IV).Subsequent chlorination of (IV) with concomitant rearrangement by means of thionyl chloride in benzene produced the 3-chloropiperidine derivative (V).The reaction of (V) with 4-hydroxybenzaldehyde (VI) in the presence of K2CO3 in DMF at 80 C furnished a mixture of six- and five-membered ring products (VII) and (VIII),which were separated by column chromatography.Condensation of the required aldehyde (VIII) with thiazolidinedione (IX) using piperidinium benzoate in refluxing toluene provided the target benzylidene thiazolidine,which was finally converted to the corresponding maleate salt.

合成路线:Mesylate (I) is heated with L-prolinol (II) to furnish pyrrolidine derivative (III),which can be converted into (VII) by different ways:1) Treatment of (III) with t-BuOK and reaction with 4-fluorobenzaldehyde (IV) in DMF.2) Conversion of (III) into chloropiperidine derivative (V) by means of SOCl2 in benzene,followed by reaction with 4-hydroxyaldehyde (VI) and K2CO3 in DMF in and chromatographic separation.3) Mitsunobu reaction between (III) and 4-hydroxyaldehyde (VI) by treatment with PPh3 and DEAD in THF,followed by chromatographic separation.Derivative (VII) is condensed with 2,4-thiazolidinedione (VIII) in toluene in the presence of piperidine and benzoic acid to afford (IX),which is finally converted into its maleate form by treatment with maleic acid in Et2O.