【结 构 式】 |
【分子编号】19863 【品名】7-oxooctanamide 【CA登记号】 |
【 分 子 式 】C8H15NO2 【 分 子 量 】157.21264 【元素组成】C 61.12% H 9.62% N 8.91% O 20.35% |
合成路线1
该中间体在本合成路线中的序号:(XIII)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 |