The intermediate 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (IV) has been obtained by two different ways: The cyclization of the bicyclic isatin (I) with cyclohexanone, NH4OH and NH4OAc in methanol gives 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-carboxamide (III), which is submitted to a Hofmann rearrangement by means of Br2 and NaOH in water to yield the intermediate amine (IV). The cyclization of 2-amino-4,5-dimethylfuran-3-carbonitrile (V) with cyclohexanone (II) by means of ZnCl2 in hot xylene or nitrobenzene gives directly the intermediate amine (IV). Finally, amine (IV) is condensed with 2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (VI) by means of NaH in NMP to provide the target amide.

The intermediate 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (IV) has been obtained by two different ways: The cyclization of the bicyclic isatin (I) with cyclohexanone, NH4OH and NH4OAc in methanol gives 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-carboxamide (III), which is submitted to a Hofmann rearrangement by means of Br2 and NaOH in water to yield the intermediate amine (IV). The cyclization of 2-amino-4,5-dimethylfuran-3-carbonitrile (V) with cyclohexanone (II) by means of ZnCl2 in hot xylene or nitrobenzene gives directly the intermediate amine (IV). Finally, amine (IV) is condensed with 2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (VI) by means of NaH in NMP to provide the target amide.