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【结 构 式】

【分子编号】68343

【品名】2,6-diethyl-4-pyridinol;2,6-diethylpyridin-4-ol

【CA登记号】 

【 分 子 式 】C9H13NO

【 分 子 量 】151.20836

【元素组成】C 71.49% H 8.67% N 9.26% O 10.58%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XVI)

The precursor 4-bromo-2,6-diethylpyridine (V) can be prepared by several methods. Condensation of 3-oxoglutaric acid (XIII) with propionic anhydride (XIV) in the presence of H2SO4, followed by cyclization with HCl at 100 °C leads to 2,6-diethyl-4-pyranone (XV). Subsequent treatment of pyranone (XV) with NH4OH at 50 °C yields 2,6-diethyl-4-pyridinol (XVI) , which is finally brominated with PBr5 in CHCl3 or POBr3 in DMF at 120 °C .
Alternatively, substitution of 2,6-dichloropyridine (XVII) with ethylmagnesium bromide (XVIII) in the presence of NiCl2(dppp) in Et2O gives 2,6-diethylpyridine (XIX), which can also be obtained by Wolff- Kishner reduction of 2,6-diacetylpyridine (XX) with NH2NH2 in the presence of NaOH in diethylene glycol at 120 °C. Oxidation of 2,6-diethylpyridine (XIX) with mCPBA in CHCl3, followed by nitration of the resulting 2,6-diethylpyridine-1-oxide (XXI) with HNO3 and H2SO4 at 90 °C provides the 4-nitro derivative (XXII). Substitution of nitropyridine (XXII) using AcBr in AcOH at 90 °C affords 4-bromo-2,6-diethylpyridin-1-oxide (XXIII), which is finally reduced with PBr3 in CH2Cl2 .

1 Gonzalez, J., Jewell, T.M., Li, H., Linton, A., Tatlock, J.H. (Pfizer, Inc.; Agouron Pharmaceuticals, Inc.). Inhibitors of hepatitis C virus RNAdependent RNA polymerase, and compositions and treatments using the same. EP 1781662, JP 2008509984, US 2006122399, US 7151105, US 8268835, WO 2006018725.
2 Li, H., Tatlock, J., Linton, A. et al. Discovery of (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-(1,2,4)triazolo(1,5-a)pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor. J Med Chem 2009, 52(5): 1255-8.
3 Johnson, S., Drowns, M., Tatlock, J. et al. Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation. Synlett 2010(5): 796-800.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 68333 4-bromo-2,6-diethylpyridine 877133-54-5 C9H12BrN 详情 详情
(XIII) 15530 1,3-Acetonedicarboxylic Acid; 3-Oxopentanedioic acid;3-oxoglutaric acid 542-05-2 C5H6O5 详情 详情
(XIV) 20095 propionic anhydride 123-62-6 C6H10O3 详情 详情
(XV) 68342 2,6-diethyl-4H-pyran-4-one   C9H12O2 详情 详情
(XVI) 68343 2,6-diethyl-4-pyridinol;2,6-diethylpyridin-4-ol   C9H13NO 详情 详情
(XVII) 13573 2,6-Dichloropyridine 2402-78-0 C5H3Cl2N 详情 详情
(XVIII) 24239 bromo(ethyl)magnesium;ethylmagnesium bromide 925-90-6 C2H5BrMg 详情 详情
(XIX) 68344 2,6-diethylpyridine 935-28-4 C9H13N 详情 详情
(XX) 48515 2,6-Diacetylpyridine 1129-30-2 C9H9NO2 详情 详情
(XXI) 68345 2,6-diethylpyridine-1-oxide   C9H13NO 详情 详情
(XXII) 68346 2,6-diethyl-4-nitropyridine 1-oxide   C9H12N2O3 详情 详情
(XXIII) 68347 4-bromo-2,6-diethylpyridin-1-oxide   C9H12BrNO 详情 详情
Extended Information