合成路线: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.
参考文献标题:2,2-Dimethylchromene derivs.,preparation process and pharmaceutical compsns.containing them
文献作者:Garc韆,G.; Di Malta,a.; Gautier,P.(Sanofi-Synthabo )
参考来源:AU 8823660; EP 0312432; EP 0556872; FR 2621587; JP 1990000180
合成路线: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.
参考文献标题:Chroman derivs
文献作者:H鋟sler,G.; Gericke,R.; Wurziger,H.; Baumgarth,M.; Lues,I.; Bergmann,R.; De Peyer,J.(Merck Patent GmbH)
参考来源:AU 8936440; DE 3820506; EP 0346724; JP 1990040375; US 5387587
合成路线: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.
参考文献标题:Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds,new channel activators
文献作者:Bergmann,R.; Gericke,R.
参考来源:J Med Chem 1990,33(2),492-504
合成路线: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.
参考文献标题:Bimakalim
文献作者:Robinson,C.; Robinson,K.A.; Castar,J.
参考来源:Drugs Fut 1996,21(4),351
产品链接: CAS No. 117545-11-6››