(7R)-7-amino-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】20339

【品名】(7R)-7-amino-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

【CA登记号】30246-33-4

【分子式】C₁₁H₁₂N₄O₃S₃

【分子量】344.43944

【元素组成】C 38.36% H 3.51% N 16.27% O 13.94% S 27.93%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

2) The reaction of 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid (VI) with 2-O-(tert-butoxycarbonyl-L-alanyl)mandelic acid (VII) by means of triethylamine in THF gives the corresponding amide (VIII), which is then esterified with dioxolone (II) as before to afford the protected product (V), already obtained.

参考文献中间体

合成目标

【1】 Prous, J.; Castaner, J.; CEFCANEL DALOXATE HYDROCHLORIDE < Prop INNM >. Drugs Fut 1989, 14, 1, 13.
【2】 Kakeya, N.; Nishizawa, S.; Nishimura, K.; Yoshimi, A.; Tamaki, S.; Mori, T.; Kitao, K.; KY-109, A new bifunctional pro-drug of a cephalosporin. Chemistry, physico-chemical and biological properties. J Antibiot 1985, 38, 3, 380-9.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	20338	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-[[(2R)-2-([2-[(tert-butoxycarbonyl)amino]propanoyl]oxy)-2-phenylethanoyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₂H₃₅N₅O₁₁S₃	详情	详情
(VI)	20339	(7R)-7-amino-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	30246-33-4	C₁₁H₁₂N₄O₃S₃	详情	详情
(VII)	20340	(11R)-2,2,8-trimethyl-4,6,9-trioxo-11-phenyl-3,5,10-trioxa-7-azadodecan-12-oic acid		C₁₇H₂₁NO₈	详情	详情
(VIII)	20341	(7R)-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-7-[[(2R)-5,11,11-trimethyl-4,7,9-trioxo-2-phenyl-3,8,10-trioxa-6-azadodec-1-anoyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid		C₂₈H₃₁N₅O₁₀S₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

3) The reaction of the 7-aminocephem derivative (VI) with ethyl acetoacetate (IX) at room temperature gives the 3-aminocrotonate derivative (X), which is esterified with dioxolone (II) as before yielding the ester derivative (XI). The acidic (HCl) hydrolysis of (XI) in methanol-dichloromethane affords the 7-aminocephem derivative (XII) , which is finally condensed with 2-O-(tert-butoxycarbonyl-L-alanyl)mandelic acid (VII) by means of dicyclohexylcarbodiimide (DCC) in dichloromethane to yield the protected product (V), already obtained.

参考文献中间体

合成目标

【1】 Nishizawa, S.; et al. (Kyoto Pharmaceutical Industries, Ltd.); Production of cephalosporin compounds.. JP 85034975 .
【2】 Nishizawa, S.; Tamaki, S.; Kakeya, N.; Kitao, K. (Kyoto Pharmaceutical Industries, Ltd.); Cephalosporin cpds.. WO 8505360 .
【3】 Prous, J.; Castaner, J.; CEFCANEL DALOXATE HYDROCHLORIDE < Prop INNM >. Drugs Fut 1989, 14, 1, 13.
【4】 Kakeya, N.; Nishizawa, S.; Nishimura, K.; Yoshimi, A.; Tamaki, S.; Mori, T.; Kitao, K.; KY-109, A new bifunctional pro-drug of a cephalosporin. Chemistry, physico-chemical and biological properties. J Antibiot 1985, 38, 3, 380-9.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	20338	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-[[(2R)-2-([2-[(tert-butoxycarbonyl)amino]propanoyl]oxy)-2-phenylethanoyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₂H₃₅N₅O₁₁S₃	详情	详情
(VI)	20340	(11R)-2,2,8-trimethyl-4,6,9-trioxo-11-phenyl-3,5,10-trioxa-7-azadodecan-12-oic acid		C₁₇H₂₁NO₈	详情	详情
(VII)	20339	(7R)-7-amino-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	30246-33-4	C₁₁H₁₂N₄O₃S₃	详情	详情
(IX)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(X)	20343	(7R)-7-[[(Z)-4-ethoxy-1-methyl-3,4-dioxo-1-butenyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid		C₁₈H₂₀N₄O₆S₃	详情	详情
(XI)	20344	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-[[(Z)-4-ethoxy-1-methyl-3,4-dioxo-1-butenyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₃H₂₄N₄O₉S₃	详情	详情
(XII)	20345	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-amino-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₁₆H₁₆N₄O₆S₃	详情	详情

Extended Information