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Benoxaprofen, Oraflex,51234-28-7,C16-H12-Cl-N-O3,2-[2-(4-Chl

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摘 要:Benoxaprofen, Oraflex,51234-28-7,C16-H12-Cl-N-O3,2-[2-(4-Chlorophenyl)benzoxazol-5-yl]propionic acid
  • 【药物名称】Benoxaprofen, Oraflex
  • 【化学名】2-[2-(4-Chlorophenyl)benzoxazol-5-yl]propionic acid
  • 【CAS登记号】51234-28-7
  • 【结构式】Benoxaprofen, Oraflex,51234-28-7,C16-H12-Cl-N-O3,2-[2-(4-Chl--药物合成数据库
  • 【分子式】C16-H12-Cl-N-O3
  • 【分子量】301.7278
  • 【原研厂家】Lilly (Originator)
  • 【作用类别】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics
  • 【研发状态】Withdrawn-1980
  • 【合成情况】 
  • 〖来源〗J Med Chem
  • 〖合成路线〗
  • 〖标题〗2-Aryl-5-benzoxazolealkanoic acid derivatives with notable antiinflammatory activity
  • 〖合成方法〗The Sandmeyer reaction of 4-aminophenyl-alpha-methylacetonitrile (I) with NaNO2, HCl and H2SO4 gives 4-hydroxyphenyl-alpha-methylacetonitrile (II), which is nitrated with nitric acid in acetic acid yielding 4-hydroxy-3-nitrophenyl-alpha-methylacetonitrile (III). The reduction of (III) with SnCl2.2H2O and HCl in ethanol, or with H2 over Pd/C in the same solvent affords 4-hydroxy-3-aminophenyl-alpha-methylacetonitrile (IV), which is hydrolyzed with refluxing concentrated HCl to 4-hydroxy-3-aminophenyl-alpha-methylacetic acid (V). The esterification of (V) with ethanol and HCl affords the corresponding ethyl ester (VI), which is cyclized with p-chlorobenzoyl chloride (VII) in pyridine at 100 C yielding ethyl 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetate (VIII). Finally, this compound is hydrolyzed with NaOH in ethanol.
  • 〖作者〗Dunwell, D.W.; et al.
  • 〖参考〗Dunwell, D.W.; et al.; 2-Aryl-5-benzoxazolealkanoic acid derivatives with notable antiinflammatory activity. J Med Chem 1975, 18, 1, 53
  • 〖出处〗J Med Chem1975,18,(1):53
  • 〖备注〗
  • 〖来源〗Drugs Fut
  • 〖合成路线〗
  • 〖标题〗Benoxaprofen
  • 〖合成方法〗The Sandmeyer reaction of 4-aminophenyl-alpha-methylacetonitrile (I) with NaNO2, HCl and H2SO4 gives 4-hydroxyphenyl-alpha-methylacetonitrile (II), which is nitrated with nitric acid in acetic acid yielding 4-hydroxy-3-nitrophenyl-alpha-methylacetonitrile (III). The reduction of (III) with SnCl2.2H2O and HCl in ethanol, or with H2 over Pd/C in the same solvent affords 4-hydroxy-3-aminophenyl-alpha-methylacetonitrile (IV), which is hydrolyzed with refluxing concentrated HCl to 4-hydroxy-3-aminophenyl-alpha-methylacetic acid (V). The esterification of (V) with ethanol and HCl affords the corresponding ethyl ester (VI), which is cyclized with p-chlorobenzoyl chloride (VII) in pyridine at 100 C yielding ethyl 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetate (VIII). Finally, this compound is hydrolyzed with NaOH in ethanol.
  • 〖作者〗Castaer, J.; Blancafort, P.
  • 〖参考〗Castaer, J.; Blancafort, P.; Benoxaprofen. Drugs Fut 1977, 2, 9, 565
  • 〖出处〗Drugs Fut1977,2,(9):565
  • 〖备注〗Synthesis The Sandmeyer reaction of 4-aminophenyl-alpha-methylacetonitrile (I) with NaNO2, HCl and H2SO4 gives 4-hydroxyphenyl-alpha-methylacetonitrile (II), which is nitrated with nitric acid in acetic acid yielding 4-hydroxy-3-nitrophenyl-alpha-methylacetonitrile (III). The reduction of (III) with SnCl2?H2O and HCl in ethanol, or with H2 over Pd/C in the same solvent affords 4-hydroxy-3-aminophenyl-alpha-methylacetonitrile (IV), which is hydrolyzed with refluxing concentrated HCl to 4-hydroxy-3-aminophenyl-alpha-methylacetic acid (V). The esterification of (V) with ethanol and HCl affords the corresponding ethyl ester (VI), which is cyclized with p-chlorobenzoyl chloride (VII) in pyridine at 100 C yielding ethyl 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetate (VIII). Finally this compound is hydrolyzed with NaOH in ethanol (1,2). Description Cream solid, m.p. 189-90 C. Manufacturer Lilly References 1. Dunwell, D.W. et al.; 2-Aryl-5-benzoxazolealkanoic acid derivatives with notable antiinflammatory activity; J Med Chem 1975, 18(1), 53 2. Dunwell, D.W. et al. (Lilly Industries Ltd.); DE 2324443
  • 〖来源〗DE 2324443; ES 414863; FR 2184966; FR 2284592; GB 1435721; JP 49054363; JP 56167645; US 3912748
  • 〖合成路线〗
  • 〖标题〗Benzoxazole derivatives
  • 〖合成方法〗The Sandmeyer reaction of 4-aminophenyl-alpha-methylacetonitrile (I) with NaNO2, HCl and H2SO4 gives 4-hydroxyphenyl-alpha-methylacetonitrile (II), which is nitrated with nitric acid in acetic acid yielding 4-hydroxy-3-nitrophenyl-alpha-methylacetonitrile (III). The reduction of (III) with SnCl2.2H2O and HCl in ethanol, or with H2 over Pd/C in the same solvent affords 4-hydroxy-3-aminophenyl-alpha-methylacetonitrile (IV), which is hydrolyzed with refluxing concentrated HCl to 4-hydroxy-3-aminophenyl-alpha-methylacetic acid (V). The esterification of (V) with ethanol and HCl affords the corresponding ethyl ester (VI), which is cyclized with p-chlorobenzoyl chloride (VII) in pyridine at 100 C yielding ethyl 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetate (VIII). Finally, this compound is hydrolyzed with NaOH in ethanol.
  • 〖作者〗Dunwell, D.W.; et al. (Lilly Industries Ltd.)
  • 〖参考〗Dunwell, D.W.; et al. (Lilly Industries Ltd.); Benzoxazole derivatives. DE 2324443; ES 414863; FR 2184966; FR 2284592; GB 1435721; JP 49054363; JP 56167645; US 3912748
  • 〖出处〗DE 2324443; ES 414863; FR 2184966; FR 2284592; GB 1435721; JP 49054363; JP 56167645; US 3912748,,():
  • 〖备注〗
 
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