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【结 构 式】

【分子编号】37481

【品名】(6R,7R)-3-[(acetoxy)methyl]-7-([2-(2-amino-1,3-thiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

【CA登记号】

【 分 子 式 】C19H21N5O9S2

【 分 子 量 】527.53604

【元素组成】C 43.26% H 4.01% N 13.28% O 27.3% S 12.16%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

The reaction of ethyl acetoacetate (I) with NaNO2 in acetic acid-water gives ethyl 2-(hydroxyimino)-3-oxobutyrate (II), which is cyclized with thiourea (III) by means of SO2Cl2 in methylene chloride yielding ethyl 2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetate (IV). The treatment of (IV) with trityl chloride (V) and triethylamine in DMF affords ethyl 2-(hydroxyimino)-2-(2-tritylaminothiazol-4-yl)acetate (VI), which by condensation with tert-butyl 2-bromo-2-methylpropionate (VII) by means of K2CO3 in DMSO is converted into ethyl 2-(2-tert-butoxycarbonyl-2-propyloxymino)-2-(2-tritylaminothiazol-4-yl)acetate (VIII). The hydrolysis of (VIII) with NaOH in refluxing methanol gives 2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (IX), which by condensation with tert-butyl 7-aminocephalosporanate (X) by means of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide in DMF yields tert-butyl 7-[2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]cephalosporanate (XI). The hydrolysis of (XI) with trifluoroacetic acid in anisole affords 7-[2-(2-aminothiazol-4-yl)-2-(2-carboxy-2-propyloxyimino)acetamido]cephalosporanic acid (XII), which is finally treated with pyridine (A) and NaI.

1 DE 2921316 .
2 Serradell, M.N.; Blancafort, P.; Castañer, J.; Ceftazidime. Drugs Fut 1981, 6, 10, 612.
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) 29669 Pyridine 110-86-1 C5H5N 详情 详情
(I) 11819 ethyl acetoacetate; ethyl 3-oxobutanoate;Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate 141-97-9 C6H10O3 详情 详情
(II) 20853 ethyl 2-(hydroxyimino)-3-oxobutanoate;(Z)-ethyl 2-(hydroxyimino)-3-oxobutanoate C6H9NO4 详情 详情
(III) 10180 Thiourea 62-56-6 CH4N2S 详情 详情
(IV) 15889 Ethyl 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate;(Z)-ethyl 2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetate; ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetate 60845-81-0 C7H9N3O3S 详情 详情
(V) 28630 Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride 76-83-5 C19H15Cl 详情 详情
(VI) 37478 ethyl 2-(hydroxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetate C26H23N3O3S 详情 详情
(VII) 34947 tert-butyl 2-bromo-2-methylpropanoate 23877-12-5 C8H15BrO2 详情 详情
(VIII) 37479 tert-butyl 2-[([(Z)-2-ethoxy-2-oxo-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino)oxy]-2-methylpropanoate C34H37N3O5S 详情 详情
(IX) 29047 2-[[2-(tert-butoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid C32H33N3O5S 详情 详情
(X) 32660 tert-butyl (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C14H20N2O5S 详情 详情
(XI) 37480 tert-butyl (6R,7R)-3-[(acetoxy)methyl]-7-([2-[[2-(tert-butoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C46H51N5O9S2 详情 详情
(XII) 37481 (6R,7R)-3-[(acetoxy)methyl]-7-([2-(2-amino-1,3-thiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid C19H21N5O9S2 详情 详情
Extended Information