The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.

The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.

The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.

The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.

The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.