Treatment of 2,4-difluoronitrobenzene (I) with isopropylamine in the presence of K2CO3 in THF afforded 2-isopropylamino-4-fluoronitrobenzene (II). Subsequent condensation of (II) with 2,3-difluorophenylacetonitrile (III) by means of potassium tert-butoxide, followed by oxidative treatment of the intermediate nitrile (IV) with H2O2 generated benzophenone (V). The nitro group of (V) was then reduced by hydrogenation over Raney Nickel yielding diamine (VI), which was cyclized to benzimidazole (VII) upon treatment with cyanogen bromide. Addition of the lithium anion of N-methyl-N-(trimethylsilyl)acetamide to (VII) gave beta-hydroxyamide (VIII). Finally, acid promoted dehydration of (VIII) furnished the corresponding alpha,beta-unsaturated amide.

Treatment of 2,4-difluoronitrobenzene (I) with isopropylamine in the presence of K2CO3 in THF afforded 2-isopropylamino-4-fluoronitrobenzene (II). Subsequent condensation of (II) with 2,3-difluorophenylacetonitrile (III) by means of potassium tert-butoxide, followed by oxidative treatment of the intermediate nitrile (IV) with H2O2 generated benzophenone (V). The nitro group of (V) was then reduced by hydrogenation over Raney Nickel yielding diamine (VI), which was cyclized to benzimidazole (VII) upon treatment with cyanogen bromide. Addition of the lithium anion of bis(trimethylsilyl)acetamide to (VII) gave beta-hydroxyamide (VIII). Finally, acid promoted dehydration of (VIII) furnished the corresponding alpha,beta-unsaturated amide, which was isoalted as the hydrochloride salt.

Treatment of 2,4-difluoronitrobenzene (I) with cyclopentylamine (II) in the presence of K2CO3 in THF afforded 2-cyclopentylamino-4-fluoronitrobenzene (III). Subsequent condensation of (III) with 2-fluorophenylacetonitrile (IV) by means of potassium tert-butoxide, followed by oxidative treatment of the intermediate nitrile (V) with H2O2 generated benzophenone (VI). The nitro group of (VI) was then reduced by hydrogenation over Raney Nickel yielding diamine (VII), which was cyclized to benzimidazole (VIII) upon treatment with cyanogen bromide. Addition of the lithium anion of N-methyl-N-(trimethylsilyl)acetamide to (VIII) gave beta-hydroxyamide (IX). Finally, acid promoted dehydration of (IX) furnished the corresponding alpha,beta-unsaturated amide, whic was isolated as the hydrochloride salt.