【结 构 式】 |
【分子编号】39839 【品名】(6R,7R)-7-[(2,2-dimethylpropanoyl)amino]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 【CA登记号】 |
【 分 子 式 】C13H18N2O5S 【 分 子 量 】314.3624 【元素组成】C 49.67% H 5.77% N 8.91% O 25.45% S 10.2% |
合成路线1
该中间体在本合成路线中的序号:(XXIV)The hydrolysis of p-methoxybenzyl-7-aminocephalosporanate (XIV) with trifluoroacetic acid gives the corresponding tree acid (XXII), which is treated with tert-butoxycarbonylazide (F) yielding the tert-butoxycarbonylamidocephalosporanic acid (XXIII). This compound is deacetylated by treatment with citrus acetyl sterase in an aqueous phosphate buffer affording the 3-hydroxymethyl derivative (XXIV), which by reaction with chlorosulfonyl isocyanate gives the 3-carbamoyloxymethyl compound (XXV). The hydrolysis of (XXV) with TFA yields 3-carbamoyloxymethyl-7beta-amino-3-cephem-4-carboxylic acid (XXVI), which is esterified with diphenyldiazomethane in dioxane affording the benzhydryl ester (XXVII). The acylation of (XXVII) with 2-thienylcarbonyl chloride (E) in CH2Cl2 gives the acylated ester (XXVIII), which by methoxylation of (XXVIII) can also be performed through hydroxylation with phenyllithium and tert-butyl hypochlorite (G) in tert-butanol to the 7-hydroxy compound (XXXII), which is then methylated with diazomethane to (XXX). Finally, this compound is hydrolyzed with trifluoroacetic acid.
【1】 Castaner, J.; Loren, J.G.; Cefoxitin. Drugs Fut 1978, 3, 6, 434. |
【2】 Hazen, G.C. (Merck & Co., Inc.); Process for preparin cephalosporin compounds. DD 100957; ES 408969; US 3780033 . |
【3】 Christensen, B.G.; Firestone, R.A.; Process for preparing cephalosporin compounds. DD 100956; ES 408970; US 3775410 . |
【4】 Christensen, B.G.; Cama, L.D. (Merck & Co., Inc.); Process for preparing penicillin and cephalosporin compounds. FR 2163144; GB 1401060; US 3843641 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(G) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
(E) | 15673 | 2-(2-thienyl)acetyl chloride; 2-Thiopheneacetyl chloride | 39098-97-0 | C6H5ClOS | 详情 | 详情 |
(F) | 39837 | 2,2-dimethylpropanoyl azide | C5H9N3O | 详情 | 详情 | |
(XIV) | 39828 | 4-methoxybenzyl (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C18H20N2O6S | 详情 | 详情 | |
(XXII) | 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 | |
(XXIII) | 39838 | (6R,7R)-3-[(acetoxy)methyl]-7-[(2,2-dimethylpropanoyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C15H20N2O6S | 详情 | 详情 | |
(XXIV) | 39839 | (6R,7R)-7-[(2,2-dimethylpropanoyl)amino]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C13H18N2O5S | 详情 | 详情 | |
(XXV) | 39840 | (6R,7R)-3-[[(aminocarbonyl)oxy]methyl]-7-[(2,2-dimethylpropanoyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C14H19N3O6S | 详情 | 详情 | |
(XXVI) | 39805 | (6R,7R)-7-amino-3-[[(aminocarbonyl)oxy]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C9H11N3O5S | 详情 | 详情 | |
(XXVII) | 39804 | benzhydryl (6R,7R)-7-amino-3-[[(aminocarbonyl)oxy]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H21N3O5S | 详情 | 详情 | |
(XXVIII) | 39841 | benzhydryl (6R,7R)-3-[[(aminocarbonyl)oxy]methyl]-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C28H25N3O6S2 | 详情 | 详情 | |
(XXX) | 39843 | benzhydryl (6R,7S)-3-[[(aminocarbonyl)oxy]methyl]-7-methoxy-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H27N3O7S2 | 详情 | 详情 | |
(XXXII) | 39842 | benzhydryl (6R,7S)-3-[[(aminocarbonyl)oxy]methyl]-7-hydroxy-7-[[(Z)-1-methoxy-2-(2-thienyl)ethylidene]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H27N3O7S2 | 详情 | 详情 |