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【结 构 式】

【分子编号】17019

【品名】[(5R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-1,3-oxazolan-5-yl]methyl methanesulfonate

【CA登记号】174649-09-3

【 分 子 式 】C15H19FN2O6S

【 分 子 量 】374.3901432

【元素组成】C 48.12% H 5.12% F 5.07% N 7.48% O 25.64% S 8.56%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

The condensation of morpholine (I) with 3,4-difluoronitrobenzene (II) by means of diisopropylethylamine in refluxing acetonitrile gives 3-fluoro-4-(4-morpholinyl)nitrobenzene (III), which is reduced with ammonium formate over Pd/C in THF/methanol to the corresponding aniline (IV). The reaction of (IV) with benzyloxycarbonyl chloride and NaHCO3 in acetone/water yields the carbamate ester (V), which is cyclized with 2(R),3-epoxypropyl butyrate (VI) by means of butyllithium in THF affording 5(R)-(hydroxymethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]oxazolidin-2-one (VII). The reaction of (VII) with methanesulfonyl chloride and triethylamine in dichloromethane gives the mesylate (VIII), which by reaction with NaN3 in hot DMF is converted into the azide (IX). The reduction of (IX) with H2 over Pd/C in ethyl acetate affords the corresponding amine (X), which is finally acetylated with acetic anhydride and pyridine.

1 Brickner, S.J.; Hutchinson, D.K.; Barbachyn, M.R.; et al.; Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant Gram-positive bacterial infections. J Med Chem 1996, 39, 3, 673.
2 Lizondo, J.; Rabasseda, X.; Castañer, J.; Linezolid. Drugs Fut 1996, 21, 11, 1116.
3 Barbachyn, M.R.; Brickner, S.J.; Hutchinson, D.K. (Pharmacia Corp.); Substd. oxazine and thiazine oxazolidinone antimicrobials. EP 0717738; JP 1997502436; WO 9507271 .
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) 10388 Morpholine 110-91-8 C4H9NO 详情 详情
(II) 17013 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene 369-34-6 C6H3F2NO2 详情 详情
(III) 17014 4-(2-fluoro-4-nitrophenyl)morpholine C10H11FN2O3 详情 详情
(IV) 17015 3-fluoro-4-morpholinophenylamine; 3-fluoro-4-morpholinoaniline; 3-fluoro-4-(4-morpholinyl)phenylamine; 3-Fluoro-4-(4-morpholinyl)benzeneamine 93246-53-8 C10H13FN2O 详情 详情
(V) 17016 benzyl N-(3-fluoro-4-morpholinophenyl)carbamate C18H19FN2O3 详情 详情
(VI) 17017 (2S)oxiranylmethyl butyrate C7H12O3 详情 详情
(VII) 17018 (5R)-3-(3-fluoro-4-morpholinophenyl)-5-(hydroxymethyl)-1,3-oxazolan-2-one 168828-82-8 C14H17FN2O4 详情 详情
(VIII) 17019 [(5R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-1,3-oxazolan-5-yl]methyl methanesulfonate 174649-09-3 C15H19FN2O6S 详情 详情
(IX) 17020 (5R)-5-(azidomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one C14H16FN5O3 详情 详情
(X) 17021 (5S)-5-(aminomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one C14H18FN3O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

The known oxazolidine methansulfonate (I) is reacted with NaN3 in hot DMF to produce azide (II). Then, condensation of azide (II) with acetylene (III) at 90 C in a pressure vessel gives rise to the target triazole derivative.

1 Phillips, O.A.; Udo, E.E.; Ali, A.A.M.; Al-Hassawi, N.; Synthesis and antibacterial activity of 5-substituted oxazolidinones. Bioorg Med Chem 2003, 11, 1, 35.
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) 17019 [(5R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-1,3-oxazolan-5-yl]methyl methanesulfonate 174649-09-3 C15H19FN2O6S 详情 详情
(II) 17020 (5R)-5-(azidomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one C14H16FN5O3 详情 详情
(III) 23634 acetylene 74-86-2 C2H2 详情 详情
Extended Information