Reaction of salicylaldehyde (I) with iodine monochloride produced 2-hydroxy-5-iodobenzaldehyde (II), which was protected with (2-methoxyethoxy) methyl chloride to give ether (III). Reduction of the aldehyde group of (III) with NaBH4 yielded alcohol (IV) and subsequent treatment with N-bromosuccinimide and triphenylphosphine generated bromide (V). N-Boc-3-aminopyrrolidinone (VII) was prepared by cyclization of (S)-alpha-Boc-2,4-diaminobutyric acid (VI) in the presence of EDC and HOBt. Subsequent alkylation of (VII) with bromide (V) produced the N-benzylpyrrolidinone derivative (VIII). Displacement of iodide group of (VIII) by zinc cyanide gave nitrile (IX). Then, acid cleavage of both Boc and MEM protecting groups furnished intermediate (X).

Thienylacrylic acid (XII), prepared from thiophene aldehyde (XI), was activated as the mixed anhydride with ethyl chloroformate and then treated with NaN3 to yield acyl azide (XIII). Cyclization of (XIII) in the presence of Bu3P in boiling diphenyl ether generated the thienopyridine system (XIV). Chlorination of (XIV) with POCl3 afforded the chloro derivative (XV). After lithium-bromine exchange with n-butyllithium, the resulting organolithium derivative (XVI) was treated with SO2 and further oxidized to sulfonyl chloride (XVII) with SO2Cl2. Coupling of (XVII) with aminopyrrolidinone (X) yielded sulfonamide (XVIII). Conversion of the nitrile of (XVIII) to the corresponding imidate (XIX), followed by reaction with ammonia produced benzamidine (XX). Finally, hydrogenolytic dechlorination of (XX) over Pd/C provided the title compound.

Reaction of salicylaldehyde (I) with iodine monochloride produced 2-hydroxy-5-iodobenzaldehyde (II), which was protected with (2-methoxyethoxy) methyl chloride to give ether (III). Reduction of the aldehyde group of (III) with NaBH4 yielded alcohol (IV) and subsequent treatment with N-bromosuccinimide and triphenylphosphine generated bromide (V). N-Boc-3-aminopyrrolidinone (VII) was prepared by cyclization of (S)-alpha-Boc-2,4-diaminobutyric acid (VI) in the presence of EDC and HOBt. Subsequent alkylation of (VII) with bromide (V) produced the N-benzylpyrrolidinone derivative (VIII). Displacement of iodide group of (VIII) by zinc cyanide gave nitrile (IX). Then, acid cleavage of both Boc and MEM protecting groups furnished intermediate (X).

The reaction of 5-chlorothieno[3,2-b]pyridine (XI) with n-BuLi and SO2 in THF and further oxidation with SO2Cl2 gives sulfonyl chloride (XII), which was coupled with aminopyrrolidinone (X) by means of TEA in dichloromethane to yield sulfonamide (XIII). Conversion of the nitrile of (XIII) to the corresponding imidate with HCl in methanol, followed by reaction with ammonia produced benzamidine (XIV). Finally, hydrogenolytic dechlorination of (XIV) over Pd/C provided the title compound.

Thienylacrylic acid (XII), prepared from thiophene aldehyde (XI), was activated as the mixed anhydride with ethyl chloroformate and then treated with NaN3 to yield acyl azide (XIII). Cyclization of (XIII) in the presence of Bu3P in boiling diphenyl ether generated the thienopyridine system (XIV). Chlorination of (XIV) with POCl3 afforded the chloro derivative (XV). After lithium-bromine exchange with n-butyllithium, the resulting organolithium derivative (XVI) was treated with SO2 and further oxidized to sulfonyl chloride (XVII) with SO2Cl2. Coupling of (XVII) with aminopyrrolidinone (X) yielded sulfonamide (XVIII). Conversion of the nitrile of (XVIII) to the corresponding imidate (XIX), followed by reaction with ammonia produced benzamidine (XX). Finally, hydrogenolytic dechlorination of (XX) over Pd/C provided the title compound.

The reaction of 5-chlorothieno[3,2-b]pyridine (XI) with n-BuLi and SO2 in THF and further oxidation with SO2Cl2 gives sulfonyl chloride (XII), which was coupled with aminopyrrolidinone (X) by means of TEA in dichloromethane to yield sulfonamide (XIII). Conversion of the nitrile of (XIII) to the corresponding imidate with HCl in methanol, followed by reaction with ammonia produced benzamidine (XIV). Finally, hydrogenolytic dechlorination of (XIV) over Pd/C provided the title compound.