Treatment of 3,4-difluoronitrobenzene (I) with hydrazine hydrate yielded the aryl hydrazine (II), which was condensed with dialdehyde (III) to give pyrazole (IV). After reduction of the nitro group of (IV) by catalytic hydrogenation, the resulting amine (V) was protected with benzyl chloroformate to afford carbamate (VI). Subsequent treatment of (VI) with (R)-glycidyl butyrate (VII) and n-butyllithium produced the chiral oxazolidinone (VIII). The alcohol group of (VIII) was converted to mesylate (IX) and then displaced with NaN3 to give azide (X), which was reduced to amine (XI) using PPh3. Acetylation of the primary amine of (XI) with Ac2O, followed by ammonolysis of the ethyl ester furnished diamide (XII). Finally, dehydration of the primary amide of (XII) with SOCl2 provided the target nitrile.

Treatment of 3,4-difluoronitrobenzene (I) with benzylamine yielded nitroaniline (II), which was reduced to diamine (III) by hydrogenation over Pt/C. Protection of (III) with benzyl chloroformate produced the bis(carbamate) (IV). Conversion of (IV) to the chiral oxazolidinone (VI) was accomplished by treatment with (R)-glycidyl butyrate (V) and n-butyllithium. The alcohol group of (VI) was converted to mesylate (VII) and then displaced with potassium phthalimide to give (VIII). Further hydrazinolysis of (VIII), followed by acetylation of the resulting amine gave acetamide (IX). Hydrogenation of (IX) in the presence of Pd/C removed both N-benzyl and carbamate groups to give the primary amine (X). Condensation of (X) with 2,5-dimethoxytetrahydrofuran-3-carbaldehyde (XI) in refluxing AcOH furnished the required 3-formylpyrrole (XII). The resulting aldehyde (XII) was then condensed with hydroxylamine and the intermediate oxime was finally converted to the target nitrile employing PPh3 as the dehydrating agent.

Treatment of 3,4-difluoronitrobenzene (I) with hydrazine hydrate yielded the aryl hydrazine (II), which was condensed with dialdehyde (III) to give pyrazole (IV). After reduction of the nitro group of (IV) by catalytic hydrogenation, the resulting amine (V) was protected with benzyl chloroformate to afford carbamate (VI). Subsequent treatment of (VI) with (R)-glycidyl butyrate (VII) and n-butyllithium produced the chiral oxazolidinone (VIII). The alcohol group of (VIII) was converted to mesylate (IX) and then displaced with NaN3 to give azide (X), which was reduced to amine (XI) using PPh3. Acetylation of the primary amine of (XI) with Ac2O, followed by ammonolysis of the ethyl ester furnished diamide (XII). Finally, dehydration of the primary amide of (XII) with SOCl2 provided the target nitrile.

Treatment of 3,4-difluoronitrobenzene (I) with benzylamine yielded nitroaniline (II), which was reduced to diamine (III) by hydrogenation over Pt/C. Protection of (III) with benzyl chloroformate produced the bis(carbamate) (IV). Conversion of (IV) to the chiral oxazolidinone (VI) was accomplished by treatment with (R)-glycidyl butyrate (V) and n-butyllithium. The alcohol group of (VI) was converted to mesylate (VII) and then displaced with potassium phthalimide to give (VIII). Further hydrazinolysis of (VIII), followed by acetylation of the resulting amine gave acetamide (IX). Hydrogenation of (IX) in the presence of Pd/C removed both N-benzyl and carbamate groups to give the primary amine (X). Condensation of (X) with 2,5-dimethoxytetrahydrofuran-3-carbaldehyde (XI) in refluxing AcOH furnished the required 3-formylpyrrole (XII). The resulting aldehyde (XII) was then condensed with hydroxylamine and the intermediate oxime was finally converted to the target nitrile employing PPh3 as the dehydrating agent.

Treatment of 3,4-difluoronitrobenzene (I) with hydrazine hydrate yielded the aryl hydrazine (II), which was condensed with dialdehyde (III) to give pyrazole (IV). After reduction of the nitro group of (IV) by catalytic hydrogenation, the resulting amine (V) was protected with benzyl chloroformate to afford carbamate (VI). Subsequent treatment of (VI) with (R)-glycidyl butyrate (VII) and n-butyllithium produced the chiral oxazolidinone (VIII). The alcohol group of (VIII) was converted to mesylate (IX) and then displaced with NaN3 to give azide (X), which was reduced to amine (XI) using PPh3. Acetylation of the primary amine of (XI) with Ac2O, followed by ammonolysis of the ethyl ester furnished diamide (XII). Finally, dehydration of the primary amide of (XII) with SOCl2 provided the target nitrile.

Treatment of 3,4-difluoronitrobenzene (I) with benzylamine yielded nitroaniline (II), which was reduced to diamine (III) by hydrogenation over Pt/C. Protection of (III) with benzyl chloroformate produced the bis(carbamate) (IV). Conversion of (IV) to the chiral oxazolidinone (VI) was accomplished by treatment with (R)-glycidyl butyrate (V) and n-butyllithium. The alcohol group of (VI) was converted to mesylate (VII) and then displaced with potassium phthalimide to give (VIII). Further hydrazinolysis of (VIII), followed by acetylation of the resulting amine gave acetamide (IX). Hydrogenation of (IX) in the presence of Pd/C removed both N-benzyl and carbamate groups to give the primary amine (X). Condensation of (X) with 2,5-dimethoxytetrahydrofuran-3-carbaldehyde (XI) in refluxing AcOH furnished the required 3-formylpyrrole (XII). The resulting aldehyde (XII) was then condensed with hydroxylamine and the intermediate oxime was finally converted to the target nitrile employing PPh3 as the dehydrating agent.