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【结 构 式】 
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【分子编号】32761 【品名】2-hydroxy-4-oxo-4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)butyric acid 【CA登记号】 |
【 分 子 式 】C17H14N2O4 【 分 子 量 】310.30924 【元素组成】C 65.8% H 4.55% N 9.03% O 20.62% |
合成路线1
该中间体在本合成路线中的序号：(VI)The Grignard condensation of phenylethynylmagnesium bromide with acetic anhydride in THF gives 4-phenyl-3-butyn-2-one (II), which is cyclized with 1-aminopyridinium iodide (III) by means of KOH in dichloromethane yielding the pyrazolopyridine (IV). The reaction of (IV) with 2-oxoacetic acid (V) by means of acetic acid in dimethoxyethane (DME) affords the butyric acid derivative (VI), which is cyclized with hydrazine in hot DMA to give the pyridazinone (VII). The condensation of (VII) with 4-bromobutyric acid ethyl ester (VIII) by means of benzyltriethylammonium chloride in hot DME/methanol provides the butyric ester intermediate (IX), which is finally hydrolyzed with NaOH.
| 【1】 Zanka, A.; et al.; Pilot-scale synthesis of a novel non-xanthine adenosine A1 receptor antagonist. 1,3-dipolar cycloaddition of pyridine N-immine to an acetylene. Org Process Res Dev 1998, 2, 5, 320. |
| 【2】 Zanka, A.; Efficient large-scale synthesis of 4-phenyl-3-butyn-2-one, a key intermediate for a novel potent adenosine antagonist. Org Process Res Dev 1998, 2, 1, 60. |
| 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) | 32758 | bromo(2-phenylethynyl)magnesium；phenylacetylenyl magnesium bromide;(phenylethynyl)magnesium bromide | C8H5BrMg | 详情 | 详情 | |
| (II) | 32759 | 4-phenyl-3-butyn-2-one | 1817-57-8 | C10H8O | 详情 | 详情 |
| (III) | 32760 | 1-aminopyridinium iodide | C5H7IN2 | 详情 | 详情 | |
| (IV) | 32760 | 1-aminopyridinium iodide | C5H7IN2 | 详情 | 详情 | |
| (V) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (VI) | 32761 | 2-hydroxy-4-oxo-4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)butyric acid | C17H14N2O4 | 详情 | 详情 | |
| (VII) | 17984 | 6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone | C17H12N4O | 详情 | 详情 | |
| (VIII) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (IX) | 32762 | ethyl 4-[6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinyl]butanoate | C23H22N4O3 | 详情 | 详情 |