ethyl 1-[2-fluoro-4-((5R)-5-[[(methylsulfonyl)oxy]methyl]-2-oxo-1,3-oxazolidin-3-yl)phenyl]-1H-pyrazole-4-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】28512

【品名】ethyl 1-[2-fluoro-4-((5R)-5-[[(methylsulfonyl)oxy]methyl]-2-oxo-1,3-oxazolidin-3-yl)phenyl]-1H-pyrazole-4-carboxylate

【CA登记号】

【分子式】C₁₇H₁₈FN₃O₇S

【分子量】427.4103432

【元素组成】C 47.77% H 4.24% F 4.45% N 9.83% O 26.2% S 7.5%

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：(IX)

Treatment of 3,4-difluoronitrobenzene (I) with hydrazine hydrate yielded the aryl hydrazine (II), which was condensed with dialdehyde (III) to give pyrazole (IV). After reduction of the nitro group of (IV) by catalytic hydrogenation, the resulting amine (V) was protected with benzyl chloroformate to afford carbamate (VI). Subsequent treatment of (VI) with (R)-glycidyl butyrate (VII) and n-butyllithium produced the chiral oxazolidinone (VIII). The alcohol group of (VIII) was converted to mesylate (IX) and then displaced with NaN3 to give azide (X), which was reduced to amine (XI) using PPh3. Acetylation of the primary amine of (XI) with Ac2O, followed by ammonolysis of the ethyl ester furnished diamide (XII). Finally, dehydration of the primary amide of (XII) with SOCl2 provided the target nitrile.

参考文献中间体

合成目标

【1】 Genin, M.J.; et al.; Substituent effects on the antibacterial activity of novel highly potent nitrogen-bound azolylphenyl oxazolidinones. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-138.
【2】 Genin, M.J.; Hutchinson, D.K.; Allwine, D.A.; Hester, J.B.; Emmert, D.E.; Garmon, S.A.; Ford, C.W.; Zurenko, G.E.; Hamel, J.C.; Schaadt, R.D.; Stapert, D.; Yagi, B.H.; Friis, J.M.; Shobe, E.M.; Adams, W.J.; Nitrogen-carbon-linked (azolylphenyl)oxazolidinones with potent antibacterial activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 1998, 41, 26, 5144.
【3】 Anderson, D.J.; Allwine, D.A.; Genin, M.J.; et al.; Substituted effects of the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 2000, 43, 5, 953.

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)	17013	1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene	369-34-6	C₆H₃F₂NO₂	详情	详情
(II)	28506	1-(2-fluoro-4-nitrophenyl)hydrazine		C₆H₆FN₃O₂	详情	详情
(III)	28507	ethyl 2-formyl-3-oxopropanoate		C₆H₈O₄	详情	详情
(IV)	28508	ethyl 1-(2-fluoro-4-nitrophenyl)-1H-pyrazole-4-carboxylate		C₁₂H₁₀FN₃O₄	详情	详情
(V)	28509	ethyl 1-(4-amino-2-fluorophenyl)-1H-pyrazole-4-carboxylate		C₁₂H₁₂FN₃O₂	详情	详情
(VI)	28510	ethyl 1-(4-[[(benzyloxy)carbonyl]amino]-2-fluorophenyl)-1H-pyrazole-4-carboxylate		C₂₀H₁₈FN₃O₄	详情	详情
(VII)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(VIII)	28511	ethyl 1-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]-1H-pyrazole-4-carboxylate		C₁₆H₁₆FN₃O₅	详情	详情
(IX)	28512	ethyl 1-[2-fluoro-4-((5R)-5-[[(methylsulfonyl)oxy]methyl]-2-oxo-1,3-oxazolidin-3-yl)phenyl]-1H-pyrazole-4-carboxylate		C₁₇H₁₈FN₃O₇S	详情	详情
(X)	28513	ethyl 1-[4-[(5R)-5-(azidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]-1H-pyrazole-4-carboxylate		C₁₆H₁₅FN₆O₄	详情	详情
(XI)	28514	ethyl 1-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]-1H-pyrazole-4-carboxylate		C₁₆H₁₇FN₄O₄	详情	详情
(XII)	28515	1-(4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1H-pyrazole-4-carboxamide		C₁₆H₁₆FN₅O₄	详情	详情

Extended Information