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,C12H11NO2,201.2270,2,2-Dimethyl-4-oxo-6-chromanecarbonitril

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摘 要:,C12H11NO2,201.2270,2,2-Dimethyl-4-oxo-6-chromanecarbonitrile
  • 【化学名】2,2-Dimethyl-4-oxo-6-chromanecarbonitrile
  • 【CAS登记号】
  • 【结构式】,C12H11NO2,201.2270,2,2-Dimethyl-4-oxo-6-chromanecarbonitril--药物合成数据库
  • 【分子式】C12H11NO2
  • 【分子量】201.2270
  • 【来源】
  • 【合成情况】 
  • 〖目标产物〗Bimakalim, SR-44866, EMD-52692
  • 〖合成路线〗
  • 〖合成方法〗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〗Bergmann, R.; Gericke, R.; Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new channel activators. J Med Chem 1990, 33, 2, 492-504
  • 〖目标产物〗Bimakalim, SR-44866, EMD-52692
  • 〖合成路线〗
  • 〖合成方法〗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〗Robinson, C.; Robinson, K.A.; Castaer, J.; Bimakalim. Drugs Fut 1996, 21, 4, 351
  • 〖目标产物〗Bimakalim, SR-44866, EMD-52692
  • 〖合成路线〗
  • 〖合成方法〗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〗Husler, G.; Gericke, R.; Wurziger, H.; Baumgarth, M.; Lues, I.; De Peyer, J.; Bergmann, R. (Merck Patent GmbH); Chroman derivs. AU 8782689; DE 3726261; EP 0273262; JP 1988170376
  • 〖目标产物〗Bimakalim, SR-44866, EMD-52692
  • 〖合成路线〗
  • 〖合成方法〗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〗Garca, G.; Di Malta, a.; Gautier, P. (Sanofi-Synthlabo ); 2,2-Dimethylchromene derivs., preparation process and pharmaceutical compsns. containing them. AU 8823660; EP 0312432; EP 0556872; FR 2621587; JP 1990000180
  • 〖目标产物〗Bimakalim, SR-44866, EMD-52692
  • 〖合成路线〗
  • 〖合成方法〗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〗Husler, G.; Gericke, R.; Wurziger, H.; Baumgarth, M.; Lues, I.; Bergmann, R.; De Peyer, J. (Merck Patent GmbH); Chroman derivs. AU 8936440; DE 3820506; EP 0346724; JP 1990040375; US 5387587
 
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