新产品编号:1361029

Chemical Name: 5-Amino-2-[3(R)-methyl-2,6-dioxohexahydro-3-pyridinyl]-1H-isoindole-1,3(2H)-dione
项目整合开发状态: Biological Testing
项目研究机构: Massachusetts Institute of Technology (Originator), University of Tokyo (Originator)
合成路线:The esterification of 2-aminopropionic acid (I) with SOCl2 and methanol gives the methyl ester (II),whih is treated with benzaldehyde and TEA in dichloromethane yielding the benzylideneimine (III).The alkylation of (III) with N-(3-iodopropyl)phthalimide (IV) by means of LDA in THF affords the substituted pentanoate (V),which is treated with 1N HCl to give 2-amino-2-methyl-5-(phthalimido)pentanoic acid methyl ester (VI).The cyclization of (VI) by means of hydrazine and sodium methoxide in methanol yields the racemic 3-amino-3-methylpiperidin-2-one (VII),which is submitted to optical resolution with optically active binaphthyl phosphoric acid to afford 3(R)-amino-3-methy-piperidin-2-one (VIII).The reaction of (VIII) with 4-nitrophthalic anhydride (IX) in dioxane gives the amide (X),which is heated under vacuum to give the phthalimide (XI).The oxidation of (XI) with mCPBA in carbon tetrachloride yields the piperidinedione (XII),which is finally reduced at the nitro group by the usual methods.

合成路线:The esterification of 2-aminopropionic acid (I) with SOCl2 and methanol gives the methyl ester (II),whih is treated with benzaldehyde and TEA in dichloromethane yielding the benzylideneimine (III).The alkylation of (III) with N-(3-iodopropyl)phthalimide (IV) by means of LDA in THF affords the substituted pentanoate (V),which is treated with 1N HCl to give 2-amino-2-methyl-5-(phthalimido)pentanoic acid methyl ester (VI).The cyclization of (VI) by means of hydrazine and sodium methoxide in methanol yields the racemic 3-amino-3-methylpiperidin-2-one (VII),which is submitted to optical resolution with optically active binaphthyl phosphoric acid to afford 3(S)-amino-3-methylpiperidin-2-one (VIII).The reaction of (VIII) with 4-nitrophthalic anhydride (IX) in dioxane gives the amide (X),which is heated under vacuum to give the phthalimide (XI).The oxidation of (XI) with mCPBA in carbon tetrachloride yields the piperidinedione (XII),which is finally reduced at the nitro group by the usual methods.