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【结 构 式】

【分子编号】19856

【品名】methyl 5-hydroxy-4-methoxy-2-pyridinecarboxylate

【CA登记号】

【 分 子 式 】C8H9NO4

【 分 子 量 】183.1638

【元素组成】C 52.46% H 4.95% N 7.65% O 34.94%

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:(VI)

1) The reaction of 5-hydroxy-2-(hydroxymthyl)-4H-pyran-4-one (I) with benzyl chloride and NaOH gives 5-benzyloxy-2-(hydroxymethyl)-4H-pyran-4-one (II), which is oxidized with Jones reagent (CrO3/H2SO4)to the corresponding 2-carboxylic acid (III). The reaction of pyran (III) with ammonia at 90 C yields the expected pyridone (IV), which is methylated with trimethylsilyldiazomethane in methanol affording 5-benzyloxy-4-methoxypyridine-2-carboxylic acid methyl ester (V). The deprotection of (V) by hydrogenation with H2 overPd/C in methanol gives 5-hydroxy-4-methoxypyridine-2-carboxylic acid methyl ester (VI), which is submitted to radical acylation with acetaldehyde, tert-butyl peroxide and FeSO4 yielding 6-acetyl-5-hydroxy-4-methoxy-pyridine-2-carboxylic acid methyl ester (VII). The methyltaion of (VII) with trimethylsilyldiazomethane as before affords 6-acetyl-4,5-dimethoxypyridine-2-carboxylic acid methyl ester (VIII), which is brominated with pyridinium tribromide to the corresponding bromoacetyl derivative (IX). The cyclization of (IX) with 7-acetoxyoctanethiomide (X) in acetone at room temperature gives 6-[2-(6-acetoxyheptyl)thiazol-4-yl]-4,5-dimethoxypyridine-2-carboxylic acid methyl ester (XI), which is finally saponified with 0,5 N NaOH. 2) The 7-acetoxyoctanethioamide (X) has been obtained as follows: The reaction of 7-oxooctanoic acid (XIII) with ammonia and oxalyl chloride gives the corresponding amide (XIII), which is then treated with Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide) in pyridine to give the expected thioamide (X).

1 Massa, M.A.; et al.; The total synthesis of the natural product endothelin converting enzyme (ECE) inhibitor, WS75624 B. 213th ACS Natl Meet (April 13-17, San Francisco) 1997, Abst MEDI 196.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 13501 Kojic acid; 5-Hydroxy-2-(hydroxymethyl)-4H-pyran-4-one 501-30-4 C6H6O4 详情 详情
(II) 19852 5-(benzyloxy)-2-(hydroxymethyl)-4H-pyran-4-one C13H12O4 详情 详情
(III) 19853 5-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid C13H10O5 详情 详情
(IV) 19854 5-(benzyloxy)-4-oxo-1,4-dihydro-2-pyridinecarboxylic acid C13H11NO4 详情 详情
(V) 19855 methyl 5-(benzyloxy)-4-methoxy-2-pyridinecarboxylate C15H15NO4 详情 详情
(VI) 19856 methyl 5-hydroxy-4-methoxy-2-pyridinecarboxylate C8H9NO4 详情 详情
(VII) 19857 methyl 6-acetyl-5-hydroxy-4-methoxy-2-pyridinecarboxylate C10H11NO5 详情 详情
(VIII) 19858 methyl 6-acetyl-4,5-dimethoxy-2-pyridinecarboxylate C11H13NO5 详情 详情
(IX) 19859 methyl 6-(2-bromoacetyl)-4,5-dimethoxy-2-pyridinecarboxylate C11H12BrNO5 详情 详情
(X) 19860 7-amino-1-methyl-7-thioxoheptyl acetate C10H19NO2S 详情 详情
(XI) 19861 methyl 6-[2-[6-(acetoxy)heptyl]-1,3-thiazol-4-yl]-4,5-dimethoxy-2-pyridinecarboxylate C21H28N2O6S 详情 详情
(XII) 19862 7-oxooctanoic acid C8H14O3 详情 详情
(XIII) 19863 7-oxooctanamide C8H15NO2 详情 详情
(XIV) 19864 7-hydroxyoctanamide C8H17NO2 详情 详情
(XV) 19865 7-amino-1-methyl-7-oxoheptyl acetate C10H19NO3 详情 详情
Extended Information