Pyrrophenone

苯并胺,N-[[(2S,4R)-1-[2-(2,4-二氟苯甲酰)苯甲酰]-4-[(三苯甲基)硫代]-2-吡咯里丁基]甲基]-4-[(Z)-(2,4-二氧二氧基-5-噻唑烷基苯)甲基]-Chemical Name: N-[1-[2-(2,4-Difluorobenzoyl)benzoyl]-4(R)-(triphenylmethylsulfanyl)pyrrolidin-2(S)-ylmethyl]-4-(2,4-dioxothiazolidin-5-ylidenemethyl)benzamide
CAS No. 341973-06-6
项目整合开发状态: Biological Testing
项目研究机构: Shionogi (Originator)
合成路线:Conversion of 4-hydroxy-L-proline (I) into the corresponding cis-N-Boc-4-hydroxy-L-proline methyl ester (II) is performed as follows: Treatment of (I) with SOCl2 in MeOH followed by reaction with Boc2O and Et3N in EtOAc affords the corresponding protected acid chloride; then the methyl ester moiety is formed under Mitsunobu conditions with formic acid,DIAD and PPh3 in THF followed by treatment with NaOH in MeOH.The OH group of (II) is converted into thioether (IV) by first mesylation with MsCl and Et3N in toluene followed by reaction with triphenylmethanethiol (III) in THF in the presence of NaH.Reduction of the methyl ester of (IV) with LiBH4 in THF provides alcohol (V),which is mesylated with MsCl and Et3N in THF and then treated with NaN3 and HMPA to furnish azide (VI).Boc removal in (VI) is performed by treatment with HCl in EtOAc to give derivative (VII),which is then converted into compound (VIII) by condensation with 2-(2,4-difluorobenzoyl)benzoic acid (XI) by means of water-soluble carbodiimide (WSC) and HOBt in DMF (compound (XI) can be obtained by Friedel-Crafts reaction between phthalic anhydride (IX) and 1,3-difluorobenzene (X) in the presence of AlCl3).Reduction of the azido moiety of (VIII) by means of SnCl2 and NaOH in EtOH furnishes amine (XII),which is finally converted into the desired product by condensation with carboxylic acid (XIII) by means of WSC and HOBt (derivative (XIII) can be obtained by Knoevenagel reaction between 4-formyl-benzoic acid (XIV) and 2,4-thiazolidinedione (XV) in refluxing 2-methoxyethanol in the presence of piperidine).