DA-7867, -Drug Synthesis Database

【结构式】

【药物名称】DA-7867

【化学名称】N-[3-[3-Fluoro-4-[6-(1-methyl-1H-tetrazol-5-yl)pyridin-3-yl]phenyl]-2-oxooxazolidin-5(S)-ylmethyl]acetamide

【CA登记号】

【分子式】C₁₉H₁₈FN₇O₃

【分子量】411.39881

【开发单位】Dong-A (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Oxazolidinones

合成路线1 合成路线2

合成路线1

Reaction of 3-fluoroaniline (I) with benzyl chloroformate provides carbamate (II). The lithium derivative of (II) is then condensed with (R)-glycidyl butyrate (III) to yield the chiral oxazolidinone (IV). After conversion of alcohol (IV) to the corresponding mesylate (V), displacement with NaN3 in hot DMF gives rise to the alkyl azide (VI). Catalytic hydrogenation of azide (VI) furnishes amine (VII), which is further acylated with acetic anhydride, producing acetamide (VIII). Aromatic iodination of (VIII) by means of iodine monochloride in the presence of trifluoroacetic acid gives (IX). Iodide compound (IX) is then converted into the aryl stannane (X) upon treatment with hexamethyl ditin and palladium catalyst

参考文献中间体

【1】 Im, W.; Lee, T.; Cho, J.; Choi, S.; Rhee, J.; In vitro and in vivo studies of hetero-ring substituted pyridine containing oxazolidinone derivatives, including DA-7867. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1311.
【2】 Lee, J.-G.; Lee, J.-J.; Park, S.-K.; Lee, T.-H.; Leem, W.-B.; Cho, J.-H.; Choi, S.-H.; Kim, D.-G.; Sung, H.-J. (Dong-A Pharmaceutical Co., Ltd.); Novel oxazolidinone derivs. and a process for the preparation thereof. WO 0194342 .

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)	20697	3-fluoroaniline; 3-fluorophenylamine	372-19-0	C₆H₆FN	详情	详情
(II)	60314	phenylmethyl 3-fluorophenylcarbamate		C₁₄H₁₂FNO₂	详情	详情
(III)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(IV)	60315	3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₀H₁₀FNO₃	详情	详情
(V)	60316	[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate		C₁₁H₁₂FNO₅S	详情	详情
(VI)	60317	(R)-5-(azidomethyl)-3-(3-fluorophenyl)oxazolidin-2-one		C₁₀H₉FN₄O₂	详情	详情
(VII)	60318	5-(aminomethyl)-3-(3-fluorophenyl)-1,3-oxazolidin-2-one		C₁₀H₁₁FN₂O₂	详情	详情
(VIII)	60319	N-{[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide		C₁₂H₁₃FN₂O₃	详情	详情
(IX)	38138	N-[[(5S)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide		C₁₂H₁₂FIN₂O₃	详情	详情
(X)	60320	N-({3-[3-fluoro-4-(trimethylstannanyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide		C₁₅H₂₁FN₂O₃Sn	详情	详情

合成路线2

Treatment of 2,5-dibromopyridine (XI) with NaCN/CuCN gives rise to nitrile (XII). Cycloaddition of NaN3 to the cyano group of (XII) then leads to the tetrazolyl pyridine (XIII) (1). Further methylation of tetrazole (XIII) with iodomethane and KOH produces a mixture of methylated regioisomers (XIV) and (XV). The desired 2-methyl tetrazole derivative (XIV) is finally subjected to Stille coupling with the aryl stannane (X) to furnish the title compound

参考文献中间体

【1】 Im, W.; Lee, T.; Cho, J.; Choi, S.; Rhee, J.; In vitro and in vivo studies of hetero-ring substituted pyridine containing oxazolidinone derivatives, including DA-7867. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1311.
【2】 Lee, J.-G.; Lee, J.-J.; Park, S.-K.; Lee, T.-H.; Leem, W.-B.; Cho, J.-H.; Choi, S.-H.; Kim, D.-G.; Sung, H.-J. (Dong-A Pharmaceutical Co., Ltd.); Novel oxazolidinone derivs. and a process for the preparation thereof. WO 0194342 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	60320	N-({3-[3-fluoro-4-(trimethylstannanyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide		C₁₅H₂₁FN₂O₃Sn	详情	详情
(XI)	19330	2,5-dibromopyridine	624-28-2	C₅H₃Br₂N	详情	详情
(XII)	60321	5-bromo-2-pyridinecarbonitrile		C₆H₃BrN₂	详情	详情
(XIII)	60322	5-bromo-2-(1H-1,2,3,4-tetraazol-5-yl)pyridine		C₆H₄BrN₅	详情	详情
(XIV)	60323	5-bromo-2-(1-methyl-1H-1,2,3,4-tetraazol-5-yl)pyridine		C₇H₆BrN₅	详情	详情
(XV)	60324	5-bromo-2-(2-methyl-2H-1,2,3,4-tetraazol-5-yl)pyridine		C₇H₆BrN₅	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)