|
【结 构 式】 
|
【分子编号】21558 【品名】(6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 【CA登记号】 |
【 分 子 式 】C15H17N5O6S2 【 分 子 量 】427.46208 【元素组成】C 42.15% H 4.01% N 16.38% O 22.46% S 15% |
合成路线1
该中间体在本合成路线中的序号：(VI)1) The methanolysis of 3-(acetoxymethyl)-7-[4-chloro-3-oxo-2(Z)-(methoxyimino)butyrylamidol-3-cephem-4-carboxylic acid (I) with methanol and NaHCO3 gives the corresponding 3-(methoxymethyl) derivative (II), which is esterified with 1-iodoethylisopropyl carbonate (III) by means of dicyclohexylamine in DMA to afford the corresponding ester (IV). Finally, this compound is cyclized with thiourea (V) and methyl iodide in a phosphate buffer.
| 【1】 Fujimoto, K.; Nakayama, E.; Nakao, H. (Sankyo Co., Ltd.); Process for preparing 3-alkoxymethylcephalosporin derivatives. DE 3244457 . |
| 【2】 Fujimoto, K.; Ishihara, S.; Yanagisawa, H.; Ide, J.; Nakayama, E.; Nakao, H.; Sugawara, S.; Iwata, M.; Studies on orally active cephalosporin esters. J Antibiot 1987, 40, 3, 370. |
| 【3】 Castaner, J.; Serradell, M.N.; Cefpodoxime Proxetil. Drugs Fut 1988, 13, 1, 16. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 27347 | N,N-dicyclohexylamine | 101-83-7 | C12H23N | 详情 | 详情 | |
| (I) | 21554 | (6R,7R)-3-[(acetoxy)methyl]-7-[[4-chloro-2-(methoxyimino)-3-oxobutanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H16ClN3O8S | 详情 | 详情 | |
| (II) | 21555 | (6R,7R)-7-[[4-chloro-2-(methoxyimino)-3-oxobutanoyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C14H16ClN3O7S | 详情 | 详情 | |
| (III) | 15685 | 1-iodoethyl isopropyl carbonate | C6H11IO3 | 详情 | 详情 | |
| (V) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VI) | 21558 | (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H17N5O6S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)A new process for the preparation of cefpodoxime, which can be converted into cefpodoxime proxetil by known methods, has been described: The condensation of 2-(2-aminothiazol-4-yl)-2(Z)-(methoxyimino)acetic acid 2-benzothiazolyl ester (I) with (6R,7R)-7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (II) by means of an organic base such as Et3N, pyridine, N-methylpiperidine, DBU or DMAP in either THF/water, acetone/water, DMF/water, dimethylacetamide or dichloromethane directly gives cefpodoxime (III).
| 【1】 Nizar, H.; Singh, K.; Khanna, J.M.; Kumar, Y.; De, S.; Arora, R.K. (Ranbaxy Laboratories Ltd.); Process for the preparation of cefpodoxime acid. WO 0068234 . |
| 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) | 43810 | S-(1,3-benzothiazol-2-yl) 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)ethanethioate | 80756-85-0 | C13H10N4O2S3 | 详情 | 详情 |
| (II) | 43811 | (6R,7R)-7-amino-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C9H12N2O4S | 详情 | 详情 | |
| (III) | 21558 | (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H17N5O6S2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)The condensation of 7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (I) with 4-bromo-2-(methoxyimino)-3-oxobutyric acid (II) by means of PCl5 and HMDS in dichloromethane gives the butyramide (III), which is cyclized with thiourea (IV) by means of Na-OAc in water to yield the thiazol derivative (IV). Finally, the carboxy group of (IV) is esterified with 1-iodoethyl isopropyl carbonate (VI) by means of DBU in DMA to afford the target cefpodoxime proxetil.
| 【1】 Kumar, Y.; Nizar, H.; Tewari, N.; Rai, B.P.; Aryan, R.C. (Ranbaxy Laboratories Ltd.); Process for the preparation of cefpodoxime acid. WO 0283634 . |
| 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) | 43811 | (6R,7R)-7-amino-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C9H12N2O4S | 详情 | 详情 | |
| (II) | 58114 | 4-bromo-2-(methoxyimino)-3-oxobutanoic acid;(Z)-4-bromo-2-(methoxyimino)-3-oxobutanoic acid | C5H6BrNO4 | 详情 | 详情 | |
| (III) | 58115 | (6R,7R)-7-{[4-bromo-2-(methoxyimino)-3-oxobutanoyl]amino}-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C14H16BrN3O7S | 详情 | 详情 | |
| (IV) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (V) | 21558 | (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H17N5O6S2 | 详情 | 详情 | |
| (VI) | 58116 | isopropyl 3-iodobutanoate | C7H13IO2 | 详情 | 详情 |