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项目整合精选>>>Ertapenem sodium, MK-0826, MK-826, ZD-4433, L-749345, Invanz
Ertapenem sodium, MK-0826, MK-826, ZD-4433, L-749345, Invanz
厄他培南钠 尔他培南钠 厄他培南Chemical Name: (1R,5S,6S)-2-[2(S)-[N-(3-Carboxyphenyl)carbamoyl]pyrrolidin-4(S)-ylsulfanyl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid monosodium salt; (4R,5S,6S)-3-[2(S)-[N-(3-Carboxyphenyl)carbamoyl]pyrrolidin-4(S)-ylsulfanyl]-6-[1(R)-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid monosodium salt
CAS No. 153832-38-3, 153773-82-1 (disodium salt), 153832-46-3 (free acid)
项目整合开发状态: Launched-2002
项目研究机构: AstraZeneca (Originator), Merck & Co. (Licensee)
合成路线:MK-0826 can be synthesized as follows: The cyclization of 2-diazo-4-[3-(1-hydroxyethyl)-4-oxoazetidin-2-yl]-3-oxopentanoic acid allyl ester (I) by means of rhodium octanoate gives the 2-oxocarbapenam derivative (II),which by reaction with chlorophosphoric acid diphenyl ester (III) and DIEA in acetonitrile yields the enol phosphate (IV).Condensation of (IV) with the sulfanylpyrrolidine (V) by means of DIEA in acetonitrile affords the corresponding addition compound MK-0826 diallyl ester (VI),which is finally deprotected by means of Meldrum's acid and Pd(PPh3)4 in DMF/THF and converted to the sodium salt.
合成路线:The sulfanylpyrrolidine (V) can be obtained as follows: Esterification of 3-nitrobenzoic acid (VII) with allyl bromide and K2CO3 in DMF gives the corresponding allyl ester (VIII),which is reduced with SnCl2 in refluxing ethyl acetate to yield the 3-aminobenzoate (IX).The condensation of (IX) with the pyrrolidinecarbonyl chloride (X),obtained from the corresponding carboxylic acid (XI) and oxalyl chloride,by means of NMM in dichloro-methane affords the expected amide (XII),which is finally deacetylated with NaOH in allyl alcohol.
📌 参考资料/链接：
参考文献标题:Carbapenems containing a carboxy substd.phenyl group,processes for their preparation,intermediates and use as antibiotics
文献作者:Betts,M.J.; Davies,G.M.; Swain,M.L.(AstraZeneca plc)
参考来源:EP 0579826; JP 1994506704; US 5478820; US 5652233; US 5856321; WO 9315078
📄 详细内容
合成路线:MK-0826 can be synthesized as follows: The cyclization of 2-diazo-4-[3-(1-hydroxyethyl)-4-oxoazetidin-2-yl]-3-oxopentanoic acid allyl ester (I) by means of rhodium octanoate gives the 2-oxocarbapenam derivative (II),which by reaction with chlorophosphoric acid diphenyl ester (III) and DIEA in acetonitrile yields the enol phosphate (IV).Condensation of (IV) with the sulfanylpyrrolidine (V) by means of DIEA in acetonitrile affords the corresponding addition compound MK-0826 diallyl ester (VI),which is finally deprotected by means of Meldrum's acid and Pd(PPh3)4 in DMF/THF and converted to the sodium salt.
参考文献标题:Process for synthesizing carbapenem antibiotics
文献作者:Houghton,P.; Williams,J.M.; Skerlj,R.; Brands,K.M.J.(Merck & Co.,Inc.)
参考来源:WO 9945010
合成路线:MK-0826 can be synthesized as follows: The cyclization of 2-diazo-4-[3-(1-hydroxyethyl)-4-oxoazetidin-2-yl]-3-oxopentanoic acid allyl ester (I) by means of rhodium octanoate gives the 2-oxocarbapenam derivative (II),which by reaction with chlorophosphoric acid diphenyl ester (III) and DIEA in acetonitrile yields the enol phosphate (IV).Condensation of (IV) with the sulfanylpyrrolidine (V) by means of DIEA in acetonitrile affords the corresponding addition compound MK-0826 diallyl ester (VI),which is finally deprotected by means of Meldrum's acid and Pd(PPh3)4 in DMF/THF and converted to the sodium salt.
合成路线:The sulfanylpyrrolidine (V) can be obtained as follows: Esterification of 3-nitrobenzoic acid (VII) with allyl bromide and K2CO3 in DMF gives the corresponding allyl ester (VIII),which is reduced with SnCl2 in refluxing ethyl acetate to yield the 3-aminobenzoate (IX).The condensation of (IX) with the pyrrolidinecarbonyl chloride (X),obtained from the corresponding carboxylic acid (XI) and oxalyl chloride,by means of NMM in dichloro-methane affords the expected amide (XII),which is finally deacetylated with NaOH in allyl alcohol.
参考文献标题:MK-0826
文献作者:Leeson,P.A.; Rabasseda,X.; Castar,J.; Sorbera,L.A.
参考来源:Drugs Fut 2000,25(8),795