Yaozh News Star Club Edu BBS TOP100 Customer Service APP
Iphone Download Android Download
  • English
  • 简体中文
Login Register
Search
Current Location： Home > Feedback Help Print

【结 构 式】

【分子编号】32659

【品名】2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl chloride

【CA登记号】75532-64-8

【 分 子 式 】C8H7Cl2N3O3S

【 分 子 量 】296.1334

【元素组成】C 32.45% H 2.38% Cl 23.94% N 14.19% O 16.21% S 10.83%
与该中间体有关的原料药合成路线共 3 条
合成路线1合成路线2合成路线3

合成路线1

该中间体在本合成路线中的序号：(VII)

The methylation of ethyl 3-oxo-2-hydroxyiminobutyrate (I) with dimethyl sulfate and Na2CO3 in methanol gives ethyl 3-oxo-2-methoxyiminobutyrate (II), which is brominated with Br2 in CHCl3 to afford ethyl 4-bromo-3-oxo-2-methoxyiminobutyrate (III). The cyclization of (III) with thiourea (A) in refluxing ethanol affords ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (IV), which is acylated with chloroacetyl chloride in dimethylacetamide to yield ethyl 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetate (V). The hydrolysis of (V) with KOH in ethanol-water gives the corresponding free acid (VI), which is treated with PCl5 in methylene chloride to obtain the acyl chloride (VII). The condensation of tert-butyl 7-aminocephalosporanate (VIII) with (VII) by means of pyridine in methylene chloride gives tert-butyl 7-[alpha-methoxyimino-(2-chloroacetamidothiazol-4-yl)acetamido]cephalosporanate (IX), which is desacylated with thiourea and triethylbenzylammonium bromide in THF-ethanol yielding tert-butyl 7-[alpha-methoxyimino-alpha-(2-aminothiazol-4-yl)acetamido]cephalosporanate (X), which is hydrolyzed with trifluoroacetic acid to afford the free cephalosporanic acid (Xl). Finally, this compound is condensed with 1-methyl-5-mercaptotetrazol (XII) by means of NaHCO3 and triethylbenzylammoniurn bromide in water.

参考文献 中间体
合成目标
【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】 Ochiai, M.; et al. (Takeda Chemical Industries, Ltd.); Thiazolylacetamido cephasloporin type compounds. DE 2556736; ES 464772; FR 2294690; GB 1536283; NL 7514811; US 4098888 .
【4】 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
(I) 20853 ethyl 2-(hydroxyimino)-3-oxobutanoate；(Z)-ethyl 2-(hydroxyimino)-3-oxobutanoate C6H9NO4 详情 详情
(II) 20854 ethyl 2-(methoxyimino)-3-oxobutanoate C7H11NO4 详情 详情
(III) 10181 ethyl 4-bromo-2-(methoxyimino)-3-oxobutanoate 60845-87-6 C7H10BrNO4 详情 详情
(IV) 10182 Ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate; ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetate; 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic acid ethyl ester 64485-88-7 C8H11N3O3S 详情 详情
(V) 20859 ethyl 2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetate C10H12ClN3O4S 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
(VIII) 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
(IX) 32661 tert-butyl (6R,7R)-3-[(acetoxy)methyl]-7-[[2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C22H26ClN5O8S2 详情 详情
(X) 32662 tert-butyl (6R,7R)-3-[(acetoxy)methyl]-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C20H25N5O7S2 详情 详情
(XI) 29686 (6R,7R)-3-[(acetoxy)methyl]-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid C16H17N5O7S2 详情 详情
(XII) 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：(VII)

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.

参考文献 中间体
合成目标
【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3

该中间体在本合成路线中的序号：(VIII)

The reaction of methylhydrazin (I) with potassium thiocyanate (II) gives N-methyl-N-aminothiourea (III), which is cyclized with dimethyl oxalate (IV) by means of sodium methoxide in methanol to afford 2,5-dihydro-6-hydroxy-2-methyl-3-mercapto-5-oxo-1,2,4-triazine (V). The reaction of (V) with 7-aminocephalosporanic acid (VI) in a buffer solution at pH 6.5 gives 7-amino-3,4-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (VII), which is condensed with 2-(2-chloroacetamido-4-thiazolyl)-2-[(Z)-methoxyimino]acetyl chloride (VIII) at pH 2 yielding 7-]2-(2-chloroacetamido-4-thiazolyl)-2-[(Z)-methoxyimino]acetamido-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (IX). Finally, this compound is hydrolyzed and treated with sodium hydroxide.

参考文献 中间体
合成目标
【1】 Neuman, M.; Cefatriaxon. Drugs Fut 1981, 6, 3, 132.
【2】 Reiner, R.; et al.; Ro-13-9904/001, a novel potent and long-acting parenteral cephalosporin. J Antibiot 1980, 32, 7, 783-786.
【3】 Reiner, R.; Montavon, M. (F. Hoffmann-La Roche AG); Cephalosporin derivs. and process for their preparation. DE 2922036 .
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) 12091 1-Methylhydrazine; Monomethyl hydrazine 60-34-4 CH6N2 详情 详情
(II) 37410 Potassium thiocyanate 333-20-0 CKNS 详情 详情
(III) 37411 1-methyl-1-hydrazinecarbothioamide C2H7N3S 详情 详情
(IV) 37412 methyl 2-methoxy-2-oxoacetate;dimethyl oxalate;Methyl oxalate 553-90-2 C4H6O4 详情 详情
(V) 37413 6-hydroxy-2-methyl-3-sulfanyl-1,2,4-triazin-5(2H)-one C4H5N3O2S 详情 详情
(VI) 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
(VII) 37414 (6R,7R)-7-amino-3-[[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid C12H13N5O5S2 详情 详情
(VIII) 32659 2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl chloride 75532-64-8 C8H7Cl2N3O3S 详情 详情
(IX) 37415 (6R,7R)-7-[[2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-(methoxyimino)acetyl]amino]-3-[[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid C20H19ClN8O8S3 详情 详情
Extended Information