The title compound has been synthesized by two closely related methods. Claisen condensation of 3,4-dimethoxyphenylacetonitrile (I) with ethyl formate produced the cyano aldehyde sodium enolate (II), which was further O-acylated with benzenesulfonyl chloride to afford (III). The aminothiophene derivative (V) was prepared by cyclization of (III) with methyl thioglycolate (IV) under basic conditions. A pyrrole ring was then introduced in (V) through a Paal-Knorr synthesis employing 2,5-dimethoxytetrahydrofuran (VI) in the presence of 4-chloropyridinium chloride, yielding (VII). Refluxing of ester (VII) in pyrrolidine (VIII) gave rise to amide (IX). The intramolecular cyclization of (IX) under Vilsmeier conditions furnished the tricyclic system (X). Finally, regioselective cleavage of the meta methoxy group of (X) by means of AlCl3 yielded the target compound.

In an alternative procedure, isovanillin (XI) was protected by O-benzylation, giving (XII), and its aldehyde group was subsequently reduced to alcohol (XIII) with NaBH4. The benzylic alcohol (XIII) was chlorinated to (XIV), which was converted to nitrile (XV) by chloride displacement with tetraethylammonium cyanide. Nitrile (XV) was subjected to Claisen condensation with ethyl formate, yielding (XVI), followed by sulfonylation with benzenesulfonyl chloride to afford (XVII), which was cyclized to the amino thiophene (XVIII) by treatment with ethyl thioglycolate (IV) as above. Condensation of (XVIII) with 2,5-dimethoxytetrahydrofuran (VI) produced the corresponding pyrrole derivative (XIX). After conversion of the ester group of (XIX) to amide (XX) upon heating with pyrrolidine (VIII), its cyclization with POCl3 furnished the thienopyrrolizinone (XXI). The O-benzyl protecting group of (XXI) was finally cleaved by treatment with HBr in HOAc.