(6R,7R)-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(hydroxyimino)acetamido]-3-[2-oxo-1-(3(R)-pyrrolidinyl)pyrrolidin-3-ylidenemethyl]-3-cephem-4-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】25502

【品名】(6R,7R)-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(hydroxyimino)acetamido]-3-[2-oxo-1-(3(R)-pyrrolidinyl)pyrrolidin-3-ylidenemethyl]-3-cephem-4-carboxylic acid

【CA登记号】

【分子式】C₂₀H₂₂N₈O₆S₂

【分子量】534.577

【元素组成】C 44.94% H 4.15% N 20.96% O 17.96% S 12%

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：(XIV)

Intermediate (VIII) is treated with TFA and anisole in dichloromethane to deprotect the 7-amino group giving (IX). The condensation of (IX) with 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(trityloxyimino)thioacetic acid S-(benzothiazol-2-yl)ester (XII) in DMF gives the expected 4-acetamido derivative (XIII), which is deprotected first with bis(trimethylsilyl)acetamide (BSA) and bis(triphenylphosphine)palladium dichloride in dichloromethane to eliminate the allyloxycarbonyl group, and then with TFA and triethylsilane to eliminate the trityl group affording Ro-63-9141 (XIV).

参考文献中间体

合成目标

【1】 Hebeisen, P.; Weiss, U.; Angehrn, P.; Runtz, V.; Kansy, M.; Heinze-Krauss, I.; Page, M.; Synthesis and SAR of pyrrolidinone-3-ylidenmethyl cephems against methicillin-resistant Staphylococcus aureus. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-21.
【2】 Page, M.; Hebeisen, P.; Angehrn, P.; Heinze-Krauss, I.; Runtz, V. (F. Hoffmann-La Roche AG); Vinyl pyrrolidine cephalosporins with basic substitutents . EP 0849269; US 5981519 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIII)	25496	(6R,7R)-3-[1-[1-(Allyloxycarbonyl)pyrrolidin-3(R)-yl]-2-oxopyrrolidin-3-ylidenemethyl]-7-(tert-butoxycarbonylmino)-3-cephem-4-carboxylic acid dibenzyl ester	C₃₈H₄₂N₄O₈S	详情	详情
(IX)	25497	(6R,7R)-3-[1-[1-(Allyloxycarbonyl)pyrrolidin-3(R)-yl]-2-oxopyrrolidin-3-ylidenemethyl]-7-amino-3-cephem-4-carboxylic acid	C₂₀H₂₄N₄O₆S	详情	详情
(X)	25498	S-(1,3-benzothiazol-2-yl) 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(trityloxy)imino]ethanethioate	C₃₀H₂₁N₅O₂S₃	详情	详情
(XI)	25499	1-allyl-1-methylpyrrolidinium 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(trityloxy)imino]acetate	C₃₁H₃₃N₅O₃S	详情	详情
(XII)	25500	1,3-benzothiazol-2-ylsulfide	C₇H₄NS₂	详情	详情
(XIII)	25501	(6R,7R)-3-[1-[1-(Allyloxycarbonyl)pyrrolidin-3(R)-yl]-2-oxopyrrolidin-3-ylidenemethyl]-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(triphenylmethoxyimino)acetamido]-3-cephem-4-carboxylic acid	C₄₃H₄₀N₈O₈S₂	详情	详情
(XIV)	25502	(6R,7R)-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(hydroxyimino)acetamido]-3-[2-oxo-1-(3(R)-pyrrolidinyl)pyrrolidin-3-ylidenemethyl]-3-cephem-4-carboxylic acid	C₂₀H₂₂N₈O₆S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Finally, compound (XIV) is condensed with the mixed carbonate (XV) by literature prodedures.

参考文献中间体

合成目标

【1】 Hebeisen, P.; et al.; Synthesis, physicochemical and pharmacokinetic properties of water soluble prodrugs of Ro 63-9141/000. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-26.
【2】 Hubschwerlen, C.; Hebeisen, P.; Specklin, J.-L. (F. Hoffmann-La Roche AG); Derivs. of 3-(2-oxo-[1,3']bipyrrolidinyl-3-ylidenemethyl)-cephems. WO 9965920 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	25502	(6R,7R)-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(hydroxyimino)acetamido]-3-[2-oxo-1-(3(R)-pyrrolidinyl)pyrrolidin-3-ylidenemethyl]-3-cephem-4-carboxylic acid		C₂₀H₂₂N₈O₆S₂	详情	详情
(XV)	25503	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate		C₁₂H₉NO₈	详情	详情

Extended Information