N-({(5S)-3-[3-fluoro-4-(3-oxo-1-pyrrolidinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide -Drug Synthesis Database

【结构式】

【分子编号】61986

【品名】N-({(5S)-3-[3-fluoro-4-(3-oxo-1-pyrrolidinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide

【CA登记号】

【分子式】C₁₆H₁₈FN₃O₄

【分子量】335.3351432

【元素组成】C 57.31% H 5.41% F 5.67% N 12.53% O 19.08%

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：(XIII)

After protection of 1-benzyl-3-pyrrolidinone (I) as the corresponding ethylene ketal (II) with ethylene glycol and p-toluenesulfonic acid, N-benzyl group hydrogenolysis over Pearlman's catalyst provides the secondary amine (III). Subsequent condensation of amine (III) with 3,4-difluoronitrobenzene (IV) in hot DMF furnishes the N-aryl pyrrolidine (V). Reduction of the nitro group of (V) by transfer hydrogenation with ammonium formate and Pd/C leads to aniline (VI). This is further acylated with benzyl chloroformate producing carbamate (VII). Then, reaction of the lithium anion of carbamate (VII) with (R)-glycidyl butyrate (VIII) gives rise to oxazolidinone (IX). After conversion of alcohol (IX) to mesylate (X), the primary amine (XI) is obtained by Gabriel synthesis with potassium phthalimide, followed by hydrazinolysis. Acylation of amine (XI) with Ac2O produces amide (XII). The ethylene ketal of (XII) is then hydrolyzed with p toluenesulfonic acid in aqueous acetone, providing pyrrolidinone (XIII).

参考文献中间体

合成目标

【1】 Paget, S.; Boggs, C.; Foleno, B.; Goldschmidt, R.; Hilliard, J.; Wira, E.; Bush, K.; Macielag, M.; Synthesis and antibacterial activity of pyrrolopyrimidine oxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1318.

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)	61976	1-(Phenylmethyl)-3-pyrrolidinone; 1-Benzyl-3-pyrrolidinone; 1-Benzyl-3-pyrrolidinon; N-Benzyl-3-pyrrolidone	775-16-6	C₁₁H₁₃NO	详情	详情
(II)	61977	7-benzyl-1,4-dioxa-7-azaspiro[4.4]nonane		C₁₃H₁₇NO₂	详情	详情
(III)	61978	1,4-dioxa-7-azaspiro[4.4]nonane		C₆H₁₁NO₂	详情	详情
(IV)	17013	1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene	369-34-6	C₆H₃F₂NO₂	详情	详情
(V)	61979	7-(2-fluoro-4-nitrophenyl)-1,4-dioxa-7-azaspiro[4.4]nonane		C₁₂H₁₃FN₂O₄	详情	详情
(VI)	61980	4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenylamine; 4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluoroaniline		C₁₂H₁₅FN₂O₂	详情	详情
(VII)	61981	benzyl 4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenylcarbamate		C₂₀H₂₁FN₂O₄	详情	详情
(VIII)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(IX)	61982	(5R)-3-[4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₆H₁₉FN₂O₅	详情	详情
(X)	61983	{(5R)-3-[4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl methanesulfonate		C₁₇H₂₁FN₂O₇S	详情	详情
(XI)	61984	(5S)-5-(aminomethyl)-3-[4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenyl]-1,3-oxazolidin-2-one		C₁₆H₂₀FN₃O₄	详情	详情
(XII)	61985	N-({(5S)-3-[4-(1,4-dioxa-7-azaspiro[4.4]non-7-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide		C₁₈H₂₂FN₃O₅	详情	详情
(XIII)	61986	N-({(5S)-3-[3-fluoro-4-(3-oxo-1-pyrrolidinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide		C₁₆H₁₈FN₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Condensation of pyrrolidinone (XIII) with methoxy-bis(dimethylamino)methane gives the beta-ketoenamine (XIV). Then, cyclization of (XIV) with 2 amidinopyridine (XV) generates the target pyrrolopyrimidine system.

参考文献中间体

合成目标

【1】 Paget, S.; Boggs, C.; Foleno, B.; Goldschmidt, R.; Hilliard, J.; Wira, E.; Bush, K.; Macielag, M.; Synthesis and antibacterial activity of pyrrolopyrimidine oxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1318.
【2】 Hlasta, D.; Paget, S. (Ortho-McNeil Pharmaceutical, Inc.); Antibacterial heterobicyclic substd. phenyl oxazolidinones. EP 1206469; US 6413981; WO 0142242 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	61986	N-({(5S)-3-[3-fluoro-4-(3-oxo-1-pyrrolidinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide	C₁₆H₁₈FN₃O₄	详情	详情
(XIV)	61987	N-{[(5S)-3-(4-{3-[(Z)-(dimethylamino)methylidene]-4-oxo-1-pyrrolidinyl}-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide	C₁₉H₂₃FN₄O₄	详情	详情
(XV)	61988	2-pyridinecarboximidamide	C₆H₇N₃	详情	详情

Extended Information