(4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one -Drug Synthesis Database

【结构式】

【分子编号】30154

【品名】(4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one

【CA登记号】

【分子式】C₂₄H₃₄N₂O₇Si

【分子量】490.62874

【元素组成】C 58.75% H 6.98% N 5.71% O 22.83% Si 5.72%

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：(XLII)

Diazoketone (XXXIX), prepared by silyl protection of the precursor (XXXVIII), was cyclized in the presence of Rh(II) catalyst to produce oxocarbapenem (XL). Treatment of (XL) with Tf2O and 2,2,6,6-tetramethylpiperidine yielded vinyl triflate (XLI). Hydroxymethylation of (XLI) was then achieved by cross coupling with tributylstannylmethanol in the presence of Pd catalyst to furnish (XLII).

参考文献中间体

合成目标

【1】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXVIII)	30150	(3S,4R)-3-((1R)-1-Hydroxyethyl)-4[(1R)-1-methyl-3-diazo-3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]azetidin-2-one	137391-68-5	C₁₇H₁₈N₄O₇	详情	详情
(XXXIX)	30151	2-Diazo-3-oxo-4(R)-[3(S)-[1(R)-(triethylsilyloxy)ethyl]-4-oxoazetidin-2(R)-yl]pentanoic acid 4-nitrobenzyl ester		C₂₃H₃₂N₄O₇Si	详情	详情
(XL)	30152	(4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]heptane-3,7-dione		C₂₃H₃₂N₂O₇Si	详情	详情
(XLI)	30153	(4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl trifluoromethanesulfonate		C₂₄H₃₁F₃N₂O₉SSi	详情	详情
(XLII)	30154	(4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one		C₂₄H₃₄N₂O₇Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XLII)

Coupling of carbapenem (XLII) with sultam (VIIIb) under Mitsunobu conditions gave adduct (XLVII), which was desylilated to yield alcohol (XLVIII). Formation of the corresponding triflate, followed by condensation with bicyclic compound (XLV) provided (II), which was converted to (L) upon treatment with HCl and NaCl. The p-nitrobenzyl ester of (L) was finally deprotected by hydrogenation over Pd/C to provide the title carboxylic acid. A further procedure to obtain the target compound is to repeat the described synthesis but using carbapenem (XXXVII), instead of carbapenem (XLII).

参考文献中间体

合成目标

【1】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIIIb)	30125	6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₁₈H₂₅NO₃SSi	详情	详情
(IL)	30160	1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia	C₄₆H₅₈F₆N₆O₁₅S₃Si	详情	详情
(XLII)	30154	(4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one	C₂₄H₃₄N₂O₇Si	详情	详情
(XLV)	30156	1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate	C₉H₁₆F₃N₃O₄S	详情	详情
(XLVII)	30158	2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₄₂H₅₇N₃O₉SSi₂	详情	详情
(XLVIII)	30159	6-(2-hydroxyethyl)-2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₃₆H₄₃N₃O₉SSi	详情	详情
(L)	30161	1-(2-amino-2-oxoethyl)-4-[2-[2-([(4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]methyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl]-1,4-diazoniabicyclo[2.2.2	C₃₉H₄₄ClF₃N₆O₁₂S₂	详情	详情

Extended Information