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【结 构 式】 
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【分子编号】32643 【品名】(6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 【CA登记号】 |
【 分 子 式 】C18H19N3O7S 【 分 子 量 】421.43088 【元素组成】C 51.3% H 4.54% N 9.97% O 26.58% S 7.61% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of 7-[alpha-amino-alpha-(4-hydroxyphenyl)acetamido]cephalosporanic acid (I) with 4-hydroxy-6-methylpyridine-3-carboxylic acid N-hydroxysuccinimide ester (II) by means of triethylamine and sodium 2-ethylhexanoate in DMF chloromethaneethyl ether gives 7-[alpha-(4-hydroxy-6-methylpyridin-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]cephalosporanic acid (III), which is then treated with 1-methyl-5-mercaptotetrazol (IV) and NaHCO3 in a phosphate buffer.
| 【1】 Yamada, H.; et al. (Sumitomo Chemical Co., Ltd.); N-acylamino-alpha-arylacetamido cephalosporins and antibacterial compositions and methods containing them. DE 2539664; ES 456652; FR 2283688; GB 1510730; US 4156724 . |
| 【2】 Leeson, P.A.; Serradell, M.N.; Castaner, J.; Mealy, N.E.; Blancafort, P.; SM-1652. Drugs Fut 1980, 5, 5, 254. |
| 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) | 32643 | (6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H19N3O7S | 详情 | 详情 | |
| (II) | 32642 | 1-[[(4-hydroxy-6-methyl-3-pyridinyl)carbonyl]oxy]-2,5-pyrrolidinedione | C11H10N2O5 | 详情 | 详情 | |
| (III) | 32644 | (6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-[[(4-hydroxy-6-methyl-3-pyridinyl)carbonyl]amino]-2-(4-hydroxyphenyl)ethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C25H24N4O9S | 详情 | 详情 | |
| (IV) | 28420 | 5-Mercapto-1-methyl-1H-tetrazole; 1-Methyl-1H-1,2,3,4-tetraazol-5-ylhydrosulfide | 13183-79-4 | C2H4N4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The condensation of acetoxymethyl derivative (VI) with N-(1-methoxycarbonyl-1-propen-2-yl)-alpha-amino-p-hydroxyphenylacetic sodium salt (III) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide (A) gives 7-(alpha-amino-p-hydroxyphenylacetamido)-3-acetoxymethyl-3-cephem-4-carboxylic acid (IX), which is then condensed with acyl chloride (V) by means of K2CO3 in ethyl acetate water to afford (VII), which is then condensed with 1-methyl-5-mercapto-1H-tetrazole (VIII) by means of NaHCO3 in a phosphate buffer.
| 【1】 Saikawa, I.; et al.; Nouvelles céphaslosporines, leur procédé de préparation et leur application en thérapeutique. BE 0837682 . |
| 【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; T-1551. Drugs Fut 1979, 4, 9, 675. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 33433 | trimethyl-N-[(E)-1-methyl-2-(trimethylsilyl)ethylidene]silanamine; N-[(E)-1-methyl-2-(trimethylsilyl)ethylidene]-N-(trimethylsilyl)amine | C9H23NSi2 | 详情 | 详情 | |
| (III) | 33434 | sodium (2R)-2-(4-hydroxyphenyl)-2-[[(Z)-3-methoxy-1-methyl-3-oxo-1-propenyl]amino]ethanoate | C13H14NNaO5 | 详情 | 详情 | |
| (V) | 24305 | 4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride | 59703-00-3 | C7H9ClN2O3 | 详情 | 详情 |
| (VI) | 33436 | [(6R,7R)-7-amino-2-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl acetate | C10H14N2O4S | 详情 | 详情 | |
| (VII) | 33437 | (6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-2-(4-hydroxyphenyl)ethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C25H27N5O10S | 详情 | 详情 | |
| (VIII) | 28420 | 5-Mercapto-1-methyl-1H-tetrazole; 1-Methyl-1H-1,2,3,4-tetraazol-5-ylhydrosulfide | 13183-79-4 | C2H4N4S | 详情 | 详情 |
| (IX) | 32643 | (6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H19N3O7S | 详情 | 详情 |