allyl (4R)-2-diazo-4-[(2R,3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidinyl]-3-oxopentanoate -Drug Synthesis Database

【结构式】

【分子编号】39645

【品名】allyl (4R)-2-diazo-4-[(2R,3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidinyl]-3-oxopentanoate

【CA登记号】

【分子式】C₁₃H₁₇N₃O₅

【分子量】295.2952

【元素组成】C 52.88% H 5.8% N 14.23% O 27.09%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(I)

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.

参考文献中间体

合成目标

【1】 Betts, M.J.; Davies, G.M.; Swain, M.L. (AstraZeneca plc); Carbapenems containing a carboxy substd. phenyl group, processes for their preparation, intermediates and use as antibiotics. EP 0579826; JP 1994506704; US 5478820; US 5652233; US 5856321; WO 9315078 .
【2】 Leeson, P.A.; Rabasseda, X.; Castañer, J.; Sorbera, L.A.; MK-0826. Drugs Fut 2000, 25, 8, 795.
【3】 Houghton, P.; Williams, J.M.; Skerlj, R.; Brands, K.M.J. (Merck & Co., Inc.); Process for synthesizing carbapenem antibiotics. WO 9945010 .

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)	39645	allyl (4R)-2-diazo-4-[(2R,3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidinyl]-3-oxopentanoate		C₁₃H₁₇N₃O₅	详情	详情
(II)	32616	allyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate		C₁₃H₁₇NO₅	详情	详情
(III)	16074	Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate	2524-64-3	C₁₂H₁₀ClO₃P	详情	详情
(IV)	32617	allyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₅H₂₆NO₈P	详情	详情
(V)	39646	allyl (2S,4S)-2-([3-[(allyloxy)carbonyl]anilino]carbonyl)-4-sulfanyl-1-pyrrolidinecarboxylate		C₁₉H₂₂N₂O₅S	详情	详情
(VI)	39647	allyl (4R,5S,6S)-3-[[(3S,5S)-1-[(allyloxy)carbonyl]-5-([3-[(allyloxy)carbonyl]anilino]carbonyl)pyrrolidinyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₃₂H₃₇N₃O₉S	详情	详情

Extended Information