Regioselective Synthesis of the 5,6‐Dihydro‐4H‐furo[2,3‐c]pyrrol‐4‐one Skeleton: A New Class of Compounds

Abstract

We hereby report the first preparation of the 5,6-dihydro-4H-furo[2,3-c]pyrrol-4-one (3) and its derivatives starting from methyl 3-(methoxycarbonyl)furan-2-acetate (8). The ester functionality connected to the methylene group was regiospecifically converted to the desired monohydrazide 9. Conversion of 9 into the acyl azide 10 followed by Curtius rearrangement gave the corresponding isocyanate derivative 11 (Scheme 2). Reaction of 11 with different nucleophiles produced urethane and urea derivatives (Scheme 3). Intramolecular cyclization reactions provided the target compounds (Scheme 5). Removal of the amine-protecting group formed the title compound 3.Introduction. -Isoindolinone (¼ 2,3-dihydro-1H-isoindol-1-one; 1) derivatives show a wide range of important biological activities. A series of isoindolinone derivatives have recently been synthesized and screened. Some substituted isoindolinone derivatives have quite potent metabotropic glutamate receptor 1 antagonist activity [1]. Moreover, it has been demonstrated that some derivatives show an antipsychotic-like effect in an animal model.

Synthesis of Indolin-2-one, Isoindolin-1-one, and Indole Derivatives from Homophthalic Acid

“…Recently, we reported that the reactivity of the ester carbonyl groups in similar systems are different. 23 The ester functionality adjacent to the CH 2 group is more reactive than the other. Therefore, the regiospecific hydrolysis of the ester functionalities in 11a-c was possible.…”