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Cefotiam hydrochloride, SCE-963, CGP-14221/E, Abbott-48999, Pansporin, Halospor

盐酸头孢替安 头孢替安 Chemical Name: 7beta-[2-(2-Imino-4-thiazolin-4-yl)acetamido]-3-[1-[2-(N,N-dimethylamino)ethyl]-1H-tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid dihydrochloride; (6R,7R)-7-[2-(2-Amino-4-thiazolyl)acetamido]-3-[[[1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid dihydrochloride
CAS No. 66309-69-1, 61622-34-2 (free acid)
项目整合开发状态: Launched-1981
项目研究机构: Novartis (Originator), Takeda (Originator)
合成路线:The reaction of 7-beta-(D-5-phthalimido-5-carboxylvaleramido)-3-hydroxy-methyl-3-cephem-4-carboxylic acid (I) with diketene in CH2Cl2 gives the 3-(3-oxobutyryloxy)methyl derivative (II),which is treated with triethylamine-N,N-dimethylaniline,dimethyldichlososilane and PCl5 to obtain 7-beta-amino-3-(3-oxobutyryloxy)methyl-3-cephem-4-carboxylic acid (III).The acylation of (III) with 4-chloro-3-oxobutyryl chloride (A) and triethylamine in CH2Cl2 affords the amide (IV),which is condensed with thiourea (B) by means of NaHCO3 in acetone yielding the thiazole derivative (V).Finally,this compound is condensed with 5-mercapto-1-[2-(N,N-dimethylamino)ethyl-1H-tetrazole (VI) by means of NaHCO3 in hot water.
📌 参考资料/链接:
参考文献标题:Novel 3-acyloxymethyl-cephem compounds useful as intermediates for preparing cephalosporin antibiotics
文献作者:Tsushima,S.; et al.(Takeda Chemical Industries,Ltd.)
参考来源:DE 2607064; ES 459261; FR 2301528; GB 1544103; US 4245088

📄 详细内容


合成路线:The condensation of 7-acetoacetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid (VII) with the mercaptane (VI) by means of NaHCO3 in hot water gives 7-beta-amino-3-[1-[2-(N,N-dimethylamino)ethyl]-1H-tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid (VIII),which is then condensed with 2-aminothiazol-4-ylacetic acid (IX) by means of N-hydroxysuccinimide and dicyclohexylcarbodiimide in THF.The free amino group of (VIII) is acylated with Cl2 and diketene giving the 4-chloro-3-oxobutyramido derivative (X),which is finally cyclized with thiourea (B) by means of NaHCO3 in acetone.

参考文献标题:7-Alpha-(2-aminothiazole)acetamidocephalosporins
文献作者:Numata,M.; et al.(Takeda Chemical Industries,Ltd.)
参考来源:DE 2461478; FR 2255077; GB 1491018; NL 7416609; US 4080498; US 4421912; US 4517361


合成路线:The reaction of 7-beta-(D-5-phthalimido-5-carboxylvaleramido)-3-hydroxy-methyl-3-cephem-4-carboxylic acid (I) with diketene in CH2Cl2 gives the 3-(3-oxobutyryloxy)methyl derivative (II),which is treated with triethylamine-N,N-dimethylaniline,dimethyldichlososilane and PCl5 to obtain 7-beta-amino-3-(3-oxobutyryloxy)methyl-3-cephem-4-carboxylic acid (III).The acylation of (III) with 4-chloro-3-oxobutyryl chloride (A) and triethylamine in CH2Cl2 affords the amide (IV),which is condensed with thiourea (B) by means of NaHCO3 in acetone yielding the thiazole derivative (V).Finally,this compound is condensed with 5-mercapto-1-[2-(N,N-dimethylamino)ethyl-1H-tetrazole (VI) by means of NaHCO3 in hot water.

合成路线:The condensation of 7-acetoacetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid (VII) with the mercaptane (VI) by means of NaHCO3 in hot water gives 7-beta-amino-3-[1-[2-(N,N-dimethylamino)ethyl]-1H-tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid (VIII),which is then condensed with 2-aminothiazol-4-ylacetic acid (IX) by means of N-hydroxysuccinimide and dicyclohexylcarbodiimide in THF.The free amino group of (VIII) is acylated with Cl2 and diketene giving the 4-chloro-3-oxobutyramido derivative (X),which is finally cyclized with thiourea (B) by means of NaHCO3 in acetone.
参考文献标题:Cefotiam
文献作者:Blancafort,P.; Serradell,M.N.; Castar,J.; Roberts,P.J.
参考来源:Drugs Fut 1979,4(6),400


产品链接: CAS No. 66309-69-1››

产品链接: CAS No.61622-34-2››