公开(公告)号：US20140187788A1

公开(公告)日：2014-07-03

申请号：US14131284

申请日：2012-07-05

申请人： Jerome Yves Cassayre ,  Edouard Godineau ,  Mohamed Abdelouahab Boussemghoune ,  Helmars Smits

发明人： Jerome Yves Cassayre ,  Edouard Godineau ,  Mohamed Abdelouahab Boussemghoune ,  Helmars Smits

IPC分类号： C07D331/04 ,  C07D409/04

CPC分类号： C07D331/04 ,  C07D409/04 ,  C07D409/12

摘要： The present invention provides processes for the preparation of compounds of formula (I) including processes comprising a. reacting a a compound comprising a thietane moiety in which the carbon atom at the 3 position of the thietane moiety is bonded to a nitrogen atom; wherein the nucleophile is selected the group consisting of: N3−, a sulfonamide having two hydrogen atoms bound to the nitrogen atom, a diimide having a hydrogen atom bound to the nitrogen atom or an anion thereof, NH2OH and NH3; and b. when the nucleophile used in step a. is N3− or NH2OH, reacting the compound produced in step a. with a suitable reducing agent to give a compound of formula (I); or when the nucleophile used in step a. is a sulfonamide, reacting the compound produced in step a. with a reagent suitable for cleaving the S—N bond of the sulfonamide group to give a compound of formula (I); or when the nucleophile used in step a. is a diimide, reacting the compound produced in step a. with a reagent suitable for cleaving the C—N bond of the amide group to give a compound of formula (I). The invention also relates to intermediates useful for the preparation of compounds of formula (I).

摘要翻译： 本发明提供制备式（I）化合物的方法，包括以下步骤：a。 使含有硫杂环丁烷部分的化合物与硫原子部分3位的碳原子键合在氮原子上; 其中所述亲核试剂选自：N 3 - ，具有与氮原子结合的2个氢原子的磺酰胺，具有与氮原子结合的氢原子的二酰亚胺或其阴离子，NH 2 OH和NH 3; 和b。 当步骤a中使用亲核试剂时。 是N 3 - 或NH 2 OH，使步骤a中制备的化合物。 与合适的还原剂反应，得到式（I）化合物; 或当步骤a中使用的亲核试剂时。 是磺酰胺，使步骤a中制备的化合物反应。 用适于切割磺酰胺基团的S-N键的试剂得到式（I）化合物; 或当步骤a中使用的亲核试剂时。 是二酰亚胺，使步骤a中制备的化合物反应。 用适于切割酰胺基团的C-N键的试剂得到式（I）的化合物。 本发明还涉及可用于制备式（I）化合物的中间体。

公开(公告)号：US20130237583A1

公开(公告)日：2013-09-12

申请号：US13703630

申请日：2011-06-14

申请人： Myriem El Qacemi ,  Helmars Smits ,  Jerome Yves Cassayre ,  Nicholas Phillip Mulholland ,  Peter Renold ,  Edouard Godineau ,  Thomas Pitterna

发明人： Myriem El Qacemi ,  Helmars Smits ,  Jerome Yves Cassayre ,  Nicholas Phillip Mulholland ,  Peter Renold ,  Edouard Godineau ,  Thomas Pitterna

IPC分类号： C07D207/46 ,  C07D207/20

CPC分类号： C07D207/46 ,  A01N43/36 ,  C07D207/20 ,  C07D401/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention provides stereoselective processes for the preparation of compounds of formula (I) wherein P is phenyl, naphthyl, a 6-membered heteroaryl group containing one or two nitrogen atoms as ring members, or a 10-membered bicyclic heteroaryl group containing one or two nitrogen atoms as ring members, and wherein the phenyl, naphthyl and heteroaryl groups are optionally substituted; R1 is chlorodifluoromethyl or trifluoromethyl; R2 is optionally substituted aryl or optionally substituted heteroaryl; n is 0 or 1; including the process comprising (a-i) reacting a compound of formula II wherein P, R1 and R2 are as defined for the compound of formula I; with nitromethane in the presence a chiral catalyst to give a compound of formula III Wherein P, R1 and R2 are as defined for the compound of formula I; and (a-ii) reductively cyclising the compound of formula III to give the compound of formula I. The invention also provides intermediates useful for processes for the synthesis of compounds of formula (I).

摘要翻译： 本发明提供了制备式（I）化合物的立体选择性方法，其中P是苯基，萘基，含有一个或两个氮原子作为环成员的6元杂芳基或含有一个或多个氮原子的10元双环杂芳基 两个氮原子作为环成员，并且其中苯基，萘基和杂芳基任选被取代; R1是氯二氟甲基或三氟甲基; R2是任选取代的芳基或任选取代的杂芳基; n为0或1; 包括（a-i）使式II化合物与式Ⅰ化合物反应的方法，其中P，R 1和R 2如对式I化合物所定义; 在硝基甲烷中存在手性催化剂，得到式III化合物，其中P，R 1和R 2如式I化合物所定义; 和（a-ii）还原性环化式III化合物以得到式I化合物。本发明还提供了可用于合成式（I）化合物的方法的中间体。

公开(公告)号：US09233920B2

公开(公告)日：2016-01-12

申请号：US13703630

申请日：2011-06-14

申请人： Myriem El Qacemi ,  Helmars Smits ,  Jerome Yves Cassayre ,  Nicholas Phillip Mulholland ,  Peter Renold ,  Edouard Godineau ,  Thomas Pitterna

发明人： Myriem El Qacemi ,  Helmars Smits ,  Jerome Yves Cassayre ,  Nicholas Phillip Mulholland ,  Peter Renold ,  Edouard Godineau ,  Thomas Pitterna

IPC分类号： C07D207/46 ,  C07D207/20 ,  C07D401/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  A01N43/36

CPC分类号： C07D207/46 ,  A01N43/36 ,  C07D207/20 ,  C07D401/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention provides stereoselective processes for the preparation of compounds of formula (I) wherein P is phenyl, naphthyl, a 6-membered heteroaryl group containing one or two nitrogen atoms as ring members, or a 10-membered bicyclic heteroaryl group containing one or two nitrogen atoms as ring members, and wherein the phenyl, naphthyl and heteroaryl groups are optionally substituted; R1 is chlorodifluoromethyl or trifluoromethyl; R2 is optionally substituted aryl or optionally substituted heteroaryl; n is 0 or 1; including the process comprising (a-i) reacting a compound of formula II wherein P, R1 and R2 are as defined for the compound of formula I; with nitromethane in the presence a chiral catalyst to give a compound of formula III Wherein P, R1 and R2 are as defined for the compound of formula I; and (a-ii) reductively cyclizing the compound of formula III to give the compound of formula I. The invention also provides intermediates useful for processes for the synthesis of compounds of formula (I).

摘要翻译： 本发明提供了制备式（I）化合物的立体选择性方法，其中P是苯基，萘基，含有一个或两个氮原子作为环成员的6元杂芳基或含有一个或多个氮原子的10元双环杂芳基 两个氮原子作为环成员，并且其中苯基，萘基和杂芳基任选被取代; R1是氯二氟甲基或三氟甲基; R2是任选取代的芳基或任选取代的杂芳基; n为0或1; 包括（a-i）使式II化合物与式Ⅰ化合物反应的方法，其中P，R 1和R 2如对式I化合物所定义; 在硝基甲烷中存在手性催化剂，得到式III化合物，其中P，R 1和R 2如式I化合物所定义; 和（a-ii）将式III化合物还原性环化得到式I化合物。本发明还提供了可用于合成式（I）化合物的方法的中间体。

公开(公告)号：US09006456B2

公开(公告)日：2015-04-14

申请号：US14131284

申请日：2012-07-05

申请人： Jerome Yves Cassayre ,  Edouard Godineau ,  Mohamed Abdelouahab Boussemghoune ,  Helmars Smits

发明人： Jerome Yves Cassayre ,  Edouard Godineau ,  Mohamed Abdelouahab Boussemghoune ,  Helmars Smits

IPC分类号： C07D331/04 ,  C07D409/12 ,  C07D409/04

CPC分类号： C07D331/04 ,  C07D409/04 ,  C07D409/12

摘要： The present invention provides processes for the preparation of compounds of formula (I) including processes comprising a. reacting a compound of formula (II) with a nucleophile in the presence of water to give a compound comprising a thietane moiety in which the carbon atom at the 3 position of the thietane moiety is bonded to a nitrogen atom; wherein the nucleophile is selected the group consisting of: N3−, a sulfonamide having two hydrogen atoms bound to the nitrogen atom, a diimide having a hydrogen atom bound to the nitrogen atom or an anion thereof, NH2OH and NH3; and b. when the nucleophile used in step a. is N3− or NH2OH, reacting the compound produced in step a. with a suitable reducing agent to give a compound of formula (I); or when the nucleophile used in step a. is a sulfonamide, reacting the compound produced in step a. with a reagent suitable for cleaving the S—N bond of the sulfonamide group to give a compound of formula (I); or when the nucleophile used in step a. is a diimide, reacting the compound produced in step a. with a reagent suitable for cleaving the C—N bond of the amide group to give a compound of formula (I). The invention also relates to intermediates useful for the preparation of compounds of formula (I).

摘要翻译： 本发明提供制备式（I）化合物的方法，包括以下步骤：a。 在水存在下使式（II）化合物与亲核试剂反应，得到包含硫杂环丁烷部分的化合物，其中硫杂环丁烷部分的3位的碳原子与氮原子结合; 其中所述亲核试剂选自：N 3 - ，具有与氮原子结合的2个氢原子的磺酰胺，具有与氮原子结合的氢原子的二酰亚胺或其阴离子，NH 2 OH和NH 3; 和b。 当步骤a中使用亲核试剂时。 是N 3 - 或NH 2 OH，使步骤a中制备的化合物。 与合适的还原剂反应，得到式（I）化合物; 或当步骤a中使用的亲核试剂时。 是磺酰胺，使步骤a中制备的化合物反应。 用适于切割磺酰胺基团的S-N键的试剂得到式（I）化合物; 或当步骤a中使用的亲核试剂时。 是二酰亚胺，使步骤a中制备的化合物反应。 用适于切割酰胺基团的C-N键的试剂得到式（I）的化合物。 本发明还涉及可用于制备式（I）化合物的中间体。