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【结 构 式】 
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【分子编号】63727 【品名】N-(2-hydroxy-3-pyridinyl)-5-methyl-3-isoxazolecarboxamide 【CA登记号】 |
【 分 子 式 】C10H9N3O3 【 分 子 量 】219.19988 【元素组成】C 54.79% H 4.14% N 19.17% O 21.9% |
合成路线1
该中间体在本合成路线中的序号：(IV)Catalytic hydrogenation of 2-hydroxy-3-nitropyridine (I) in the presence of Pd/C affords 3-amino-2-hydroxypyridine (II). This is then acylated by 5-methylisoxazole-3-carbonyl chloride (III) to furnish the corresponding amide (IV). (1)
| 【1】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; Johnson, T.O. Jr. (Agouron Pharmaceuticals, Inc.); Antipicornaviral cpds. and compsns., their pharmaceutical uses, and material for their synthesis. JP 2003515591; US 2001047006; US 6514997; WO 0140189 . |
合成路线2
该中间体在本合成路线中的序号：(IV)Deprotection of N-Boc-D-3,4-difluorophenylalanine (V) by means of HCl in dioxane yields aminoacid (VI). Subsequent diazotization of (VI) with NaNO2/H2SO4 leads to hydroxyacid (VII). After esterification of (VII) with methanolic HCl, the hydroxyester (VIII) is converted into triflate (IX) upon treatment with trifluoromethanesulfonic anhydride and 2,6-lutidine. Condensation of hydroxypyridine (IV) with triflate (IX) in the presence of NaH gives rise to the N-alkylated pyridone (X). The methyl ester group of (X) is then hydrolyzed to the corresponding carboxylic acid (XI) by means of either NaOH or LiI in pyridine. (1,2)
| 【1】 Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors: 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics. J Med Chem 2002, 45, 8, 1607. |
| 【2】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; Johnson, T.O. Jr. (Agouron Pharmaceuticals, Inc.); Antipicornaviral cpds. and compsns., their pharmaceutical uses, and material for their synthesis. JP 2003515591; US 2001047006; US 6514997; WO 0140189 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 63727 | N-(2-hydroxy-3-pyridinyl)-5-methyl-3-isoxazolecarboxamide | C10H9N3O3 | 详情 | 详情 | |
| (V) | 63728 | N-{[(1,1-dimethylethyl)oxy]carbonyl}-3,4-difluorophenylalanine | C14H17F2NO4 | 详情 | 详情 | |
| (VI) | 63729 | 3,4-difluorophenylalanine | C9H9F2NO2 | 详情 | 详情 | |
| (VII) | 63730 | 3-(3,4-difluorophenyl)-2-hydroxypropanoic acid | C9H8F2O3 | 详情 | 详情 | |
| (VIII) | 63731 | methyl 3-(3,4-difluorophenyl)-2-hydroxypropanoate | C10H10F2O3 | 详情 | 详情 | |
| (IX) | 63732 | methyl 3-(3,4-difluorophenyl)-2-{[(trifluoromethyl)sulfonyl]oxy}propanoate | C11H9F5O5S | 详情 | 详情 | |
| (X) | 63733 | methyl 3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoate | C20H17F2N3O5 | 详情 | 详情 | |
| (XI) | 63734 | 3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid | C19H15F2N3O5 | 详情 | 详情 |