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【结 构 式】 
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【分子编号】32663 【品名】(6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 【CA登记号】24209-38-9 |
【 分 子 式 】C10H12N6O3S2 【 分 子 量 】328.37592 【元素组成】C 36.58% H 3.68% N 25.59% O 14.62% S 19.53% |
合成路线1
该中间体在本合成路线中的序号：(XIII)The condensation of (VII) or the free acid (VI) by means of pyridine or isobutyl chloroformate, respectively, with 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIII) gives 7-[alpha-(2-chloroacetylamidothiazol-4-yl)-alpha-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (XIV), which is finally desacylated with thiourea (A) and benzyltriethylammonium bromide as before.
| 【1】 Ochiai, M.; et al.; New cephalosporin derivatives with high antibacterial activities. Chem Pharm Bull 1977, 25, 11, 3115-17. |
| 【2】 Ochiai, M.; et al.; Cephalosporin derivatives and their preparation. BE 0853545; JP 52125188; ZA 7702030 . |
| 【3】 Serradell, M.N.; Castaner, J.; Blancafort, P.; SCE-1365. Drugs Fut 1980, 5, 3, 146. |
| 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) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VI) | 20860 | 2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetic acid | 64486-18-6 | C8H8ClN3O4S | 详情 | 详情 |
| (VII) | 32659 | 2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl chloride | 75532-64-8 | C8H7Cl2N3O3S | 详情 | 详情 |
| (XIII) | 32663 | (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 24209-38-9 | C10H12N6O3S2 | 详情 | 详情 |
| (XIV) | 32664 | (6R,7R)-7-[[2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl]amino]-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H18ClN9O6S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)By condensation of alpha-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetic acid (I) with 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (II) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide in acetonitrile.
| 【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 | |
| (I) | 33432 | (2R)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-2-(4-hydroxyphenyl)ethanoic acid | C15H17N3O6 | 详情 | 详情 | |
| (II) | 32663 | (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 24209-38-9 | C10H12N6O3S2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of N-(1-methoxycarbonyl-1-propen-2-yl)-alpha-amino-p-hydroxyphenylacetic sodium salt (III) with 7-amino-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (II) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide (A) in acetonitrile gives 7-(alpha-amino-p-hydroxy-phenylacetamido)-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (IV), which is then condensed with 4-ethyl-2,3-dioxopiperazino-1-carbonyl chloride (V) by means of K2CO3 in ethyl acetate water.
| 【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 | |
| (II) | 32663 | (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 24209-38-9 | C10H12N6O3S2 | 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 | |
| (IV) | 33435 | (6R,7R)-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H19N7O5S2 | 详情 | 详情 | |
| (V) | 24305 | 4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride | 59703-00-3 | C7H9ClN2O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The condensation of (II) with the substituted phenylacetic acid (X) by means of ethyl chlorocarbonate gives the cephalosporin (XI), which is then cyclized by means of NaH in ethanol.
| 【1】 Saikawa, I.; et al. (Toyama Chemical Co., Ltd.); Process for preparation of novel penicilins and cephalosporins. JP 52036684 . |
| 【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 |
|---|---|---|---|---|---|---|
| (II) | 32663 | (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 24209-38-9 | C10H12N6O3S2 | 详情 | 详情 |
| (X) | 33438 | (11R)-5-ethyl-11-(4-hydroxyphenyl)-1-(4-nitrophenyl)-3,4,9-trioxo-2-oxa-5,8,10-triazadodecan-12-oic acid | C22H24N4O9 | 详情 | 详情 | |
| (XI) | 33439 | (6R,7R)-7-[[(2R)-8-ethyl-2-(4-hydroxyphenyl)-12-(4-nitrophenyl)-4,9,10-trioxo-11-oxa-3,5,8-triazadodec-1-anoyl]amino]-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C32H34N10O11S2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)The formylation of 7-aminocephalosporanic acid (I) by the usual techniques produces 7-formamidocephalosporanic acid (II), which is then treated with the sodium salt of 1-methyl-1H-tetrazole-5-thiol (III) to yield 7-formamido-3-(1-methyl-1H-tetrazol-5-ylthio)methyl-3-cephem-4-carboxylic acid (IV). The resulting product (IV) is deformylated affording 7-amino-3-(1-methyl-1H-tetrazol-5-ylthio)methyl-3-cephem-4-carboxylic acid (V), which is finally acylated with anhydro-O-carboxymandelic acid (VI) using the usual techniques.
| 【1】 Castañer, J.; Cefamandole. Drugs Fut 1977, 2, 10, 646. |
| 【2】 Tensmeyer, L.G. (Eli Lilly and Company); Cefamandole derivatives. US 3947415 . |
| 【3】 Tensmeyer, L.G. (Eli Lilly and Company); Cefamandole derivatives. US 3947414 . |
| 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) | 22747 | (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C10H12N2O5S | 详情 | 详情 | |
| (II) | 40146 | (6R,7R)-3-[(acetoxy)methyl]-7-(formylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C11H12N2O6S | 详情 | 详情 | |
| (III) | 40147 | sodium 1-methyl-1H-1,2,3,4-tetraazole-5-thiolate | C2H3N4NaS | 详情 | 详情 | |
| (IV) | 40148 | (6R,7R)-7-(formylamino)-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C11H12N6O4S2 | 详情 | 详情 | |
| (V) | 32663 | (6R,7R)-7-amino-3-[[(1-methyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 24209-38-9 | C10H12N6O3S2 | 详情 | 详情 |
| (VI) | 40149 | (5R)-5-phenyl-1,3-dioxolane-2,4-dione | C9H6O4 | 详情 | 详情 |