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    • 8. 发明申请
    • A NOVEL PROCESS FOR THE PREPARATION OF LINEZOLID AND RELATED COMPOUNDS
    • 制备线性和相关化合物的新方法
    • WO2005099353A2
    • 2005-10-27
    • PCT/IN2004000105
    • 2004-04-19
    • SYMED LABS LTDMOHAN RAO DODDAKRISHNA REDDY PINGILI
    • MOHAN RAO DODDAKRISHNA REDDY PINGILI
    • C07D295/135C07D413/10C07D417/10
    • C07D413/10C07D263/20C07D295/135C07D417/10
    • The present invention provides a novel process for preparation of 5-aminomethyl substituted oxazolidinones, key intermediates for oxazolidinone antibacterials including linezolid. Thus linezolid is prepared by a) reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; b) subjecting N-[3-Chloro-2-(R)-hydroxypropyl]-3-fluoro-4-morpholinyl aniline produced above to carbonylation; c) reacting (5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone produced above with potassium phthalimide; d) reacting (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]phthalimide produced above with hydrazine hydrate; and e) reacting S-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine produced above with acetic anhydride to produce linezolid.
    • 本发明提供了一种制备5-氨基甲基取代的恶唑烷酮的新方法,包括利奈唑胺的恶唑烷酮抗菌剂的关键中间体。 因此,利奈唑胺通过以下方法制备:a)使3-氟-4-吗啉基苯胺与R-表氯醇反应; b)使上面制备的N- [3-氯-2-(R) - 羟丙基] -3-氟-4-吗啉基苯胺进行羰基化; c)使上述制备的(5R)-5-(氯甲基)-3- [3-氟-4-(4-吗啉基)苯基] -2-恶唑烷酮与邻苯二甲酰亚胺钾反应; d)使上述制备的(S)-N - [[3- [3-氟-4- [4-吗啉基]苯基] -2-氧代-5-恶唑烷基]甲基]邻苯二甲酰亚胺与水合肼反应; 和e)使上述制备的S-N - [[3- [3-氟-4- [4-吗啉基]苯基] -2-氧代-5-恶唑烷基]甲基]胺与乙酸酐反应,生成利奈唑胺。