公开(公告)号：US08420808B2

公开(公告)日：2013-04-16

申请号：US13060839

申请日：2009-01-30

申请人： Alessandro Leganza ,  Marco Galvagni

发明人： Alessandro Leganza ,  Marco Galvagni

IPC分类号： C07D265/12

CPC分类号： C07D265/18

摘要： The present invention is directed to a process for the preparation of Efavirenz, (4S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, of formula (I) comprising reacting the intermediate of formula (II) [0045] as a free base or a salt thereof, with diphosgene (TCMCF, trichlormethylchloroformate) Cl3CO—COCl in an organic solvent or in a biphasic medium comprised of an organic solvent and water, preferably but not mandatorily in the presence of a weak base in an amount sufficient to neutralise the reaction mixture or in an up to 30% molar excess of such amount.

摘要翻译： 本发明涉及制备依法韦仑，（4S）-6-氯-4-（环丙基乙炔基）-4-（三氟甲基）-1,4-二氢-2H-3,1-苯并恶嗪-2-酮的方法， 一种式（I）包括使式（II）的中间体作为游离碱或其盐与二光气（TCMCF，氯甲酸三氯甲酯）Cl 3 CO-COCl在有机溶剂中或在包含 有机溶剂和水，优选但不强制地在弱碱存在下以足以中和反应混合物的量或高达30％摩尔过量的这种量。

公开(公告)号：US20110196151A1

公开(公告)日：2011-08-11

申请号：US13060839

申请日：2009-01-30

申请人： Alessandro Leganza ,  Marco Galvagni

发明人： Alessandro Leganza ,  Marco Galvagni

IPC分类号： C07D265/12

CPC分类号： C07D265/18

摘要： The present invention is directed to a process for the preparation of Efavirenz, (4S)-6-chloro-4-(cyclopropy-lethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, of formula (I) comprising reacting the intermediate of formula (II) [0045] as a free base or a salt thereof, with diphosgene (TCMCF, trichlormethylchloroformate) Cl3CO—COCl in an organic solvent or in a biphasic medium comprised of an organic solvent and water, preferably but not mandatorily in the presence of a weak base in an amount sufficient to neutralise the reaction mixture or in an up to 30% molar excess of such amount.

摘要翻译： 本发明涉及制备依法韦仑，（4S）-6-氯-4-（环丙基 - 乙炔基）-4-（三氟甲基）-1,4-二氢-2H-3,1-苯并恶嗪-2-酮的方法， （II）的中间体与游离碱或其盐与二光气（TCMCF，氯甲酸三氯甲酯）Cl 3 CO-COCl在有机溶剂中或在双相介质中反应，式 的有机溶剂和水，优选但不强制地在弱碱存在下，其量足以中和反应混合物或至多30％摩尔过量的这种量。

公开(公告)号：US08927558B2

公开(公告)日：2015-01-06

申请号：US13470411

申请日：2012-05-14

申请人： Francesco Fontana ,  Alessandro Leganza ,  Sergio Osti

发明人： Francesco Fontana ,  Alessandro Leganza ,  Sergio Osti

IPC分类号： A61K31/517 ,  C07D405/10 ,  C07D239/94 ,  G01N30/06 ,  A61P35/04

CPC分类号： G01N30/8631 ,  C07D239/94 ,  C07D405/04 ,  G01N30/06

摘要： Impurities of lapatinib such as N-{3-chloro-4-[(2-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine compound of formula (I) or a salt thereof: and analytical methods for identifying and quantifying such impurities of Lapatinib and salts thereof are provided. Also provided is Lapatinib containing less than about 0.05 percent of this and related impurities and methods for preparing such pure forms of Lapatinib.

摘要翻译： 拉帕替尼的杂质如N- {3-氯-4 - [（2-氟苄基）氧基]苯基} -6- [5 - （{[2-（甲基磺酰基）乙基]氨基}甲基）呋喃-2-基] 喹唑啉-4-胺的式（I）化合物或其盐：提供了用于鉴定和定量这些杂质的拉帕替尼及其盐的分析方法。 还提供了含有少于约0.05％的这种和相关杂质的拉帕替尼以及制备这种纯形式的拉帕替尼的方法。

公开(公告)号：US20120295928A1

公开(公告)日：2012-11-22

申请号：US13470411

申请日：2012-05-14

申请人： Francesco Fontana ,  Alessandro Leganza ,  Sergio Osti

发明人： Francesco Fontana ,  Alessandro Leganza ,  Sergio Osti

IPC分类号： G01N30/06 ,  A61P35/04 ,  A61K31/517 ,  C07D405/10 ,  C07D239/94

CPC分类号： G01N30/8631 ,  C07D239/94 ,  C07D405/04 ,  G01N30/06

摘要： Impurities of lapatinib such as N-{3-chloro-4-[(2-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine compound of formula (I) or a salt thereof: and analytical methods for identifying and quantifying such impurities of Lapatinib and salts thereof are provided. Also provided is Lapatinib containing less than about 0.05 percent of this and related impurities and methods for preparing such pure forms of Lapatinib.

摘要翻译： 拉帕替尼的杂质如N- {3-氯-4 - [（2-氟苄基）氧基]苯基} -6- [5 - （{[2-（甲基磺酰基）乙基]氨基}甲基）呋喃-2-基] 喹唑啉-4-胺的式（I）化合物或其盐：提供了用于鉴定和定量这些杂质的拉帕替尼及其盐的分析方法。 还提供了含有少于约0.05％的这种和相关杂质的拉帕替尼以及制备这种纯形式的拉帕替尼的方法。