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1. 发明申请

WO2008031567B1 PROCESS FOR PREPARING BIARYL SUBSTITUTED 4-AMINO-BUTYRIC ACID OR DERIVATIVES THEREOF AND THEIR USE IN THE PRODUCTION OF NEP INHIBITORS 审中-公开
标题翻译：制备双芳基取代的4-氨基丁酸或其衍生物的方法及其在生产NEP抑制剂中的用途
公开(公告)号：WO2008031567B1
公开(公告)日：2008-05-08
申请号：PCT/EP2007007913
申请日：2007-09-11
申请人： NOVARTIS AG , HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
发明人： HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
IPC分类号： C07C227/16 , C07C227/32 , C07C229/34
CPC分类号： C07C269/06 , Y02P20/55 , C07C271/22
摘要： The invention relates to a process for producing a compound according to formula (i) or salt thereof, wherein R1 and R1´ are independently hydrogen or an amine protecting group and R2 is a carboxyl group or an ester group, comprising reacting a compound according to formula (ii) or salt thereof, wherein R1, R1´ and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.
摘要翻译：本发明涉及制备式（I）化合物或其盐的方法，其中R 1和R 1'独立地为氢或胺保护基，并且R 2为羧基或酯基，所述方法包括使根据式在过渡金属催化剂和手性配体存在下，使式（ⅱ）化合物或其盐（其中R1，R1'和R2如上定义）与氢反应，其中过渡金属选自元素周期表。此外，本发明涉及通过所述方法可获得的产品及其在NEP抑制剂生产中的用途。此外，本发明涉及过渡金属催化剂在制备NEP抑制剂或其前药中的用途。

2. 发明申请

WO2006111535A3 DIPHOSPHINES AND METAL COMPLEXES 审中-公开
标题翻译：二氢吡啶和金属络合物
公开(公告)号：WO2006111535A3
公开(公告)日：2006-12-28
申请号：PCT/EP2006061650
申请日：2006-04-19
申请人： UMICORE AG & CO KG , KESSELGRUBER MARTIN , THOMMEN MARC , LOTZ MATTHIAS
发明人： KESSELGRUBER MARTIN , THOMMEN MARC , LOTZ MATTHIAS
IPC分类号： C07F17/02
CPC分类号： B41K1/28 , B41K1/32 , C07F17/02
摘要： Compounds of the formula I or I', where the radicals R 1 are each, independently of one another, a hydrogen atom or C 1 -C 4 -alkyl and R' 1 is C 1 -C 4 -alkyl; X 1 and X 2 are each, independently of one another, a sec-phosphino group; R 2 is hydrogen, R 01 R 02 R 03 Si- is halogen-, hydroxyl-, C 1 -C 8 -alkoxy- or R 04 R 05 N-substituted C 1 -C 18 -acyl or is R 06 -X 01 -C(O)-; R 01 , R 02 and R 03 are each, independently of one another, C 1 -C 12 -alkyl, unsubstituted or C 1 -C 4 -alkyl- or C 1 -C 4 -alkoxy-substituted C 6 -C 10 -aryl or C 7 -C 12 -aralkyl; R 04 and R 05 are each, independently of one another, hydrogen, C 1 -C 12 -alkyl, C 3 -C 8 -cycloalkyl, C 6 -C 10 -aryl or C 7 -C 12 -aralkyl, or R 04 and R 05 together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; R 06 is C 1 -C 18 -alkyl, unsubstituted or C 1 -C 4 -alkyl- or C 1 -C 4 -alkoxy-substituted C 3 -C 8 -cycloalkyl, C 6 -C 10 -aryl or C 7 -C 12 -aralkyl; X 01 is -O- or -NH-; T is C-bonded C 3 -C 20 -heteroarylene; v is 0 or an integer from 1 to 4; X 1 in the heteroring of the heteroarylene is bound in the ortho position relative to the T-C* bond; and * indicates a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically pure diastereomers. The compounds are excellent chiral ligands for metal complexes as enantioselective catalysts for the hydrogenation of prochiral organic compounds.
摘要翻译：式I或I'的化合物，其中基团R 1各自彼此独立地为氢原子或C 1 -C 4烷基，亚烷基和R'1是C 1 -C 4 - 烷基; X 1和X 2各自彼此独立地为仲膦基; R 2是氢，R 1是R 2，R 2是卤素，羟基，C 1 -C 6烷基， C 1 -C 8烷基 - 或R 14 R 15 N-取代的C 1〜 -C（O） - ; - C 1-6烷基或-C（O） - ; R 01，R 02和R 03各自彼此独立地为C 1 -C 3 未取代的或C 1 -C 4 - 亚烷基 - 或C 1 -C 4 - / - 烷氧基取代的C 6 -C 10 - 芳基或C 7 -C 12 - 芳烷基 ; R 04和R 05各自彼此独立地为氢，C 1 -C 12 - C 12 - 烷基 C 3 -C 8 - 环烷基，C 6 -C 10 - 芳基或C 7 -C 12 - 芳烷基，或R 14和R 15一起是三亚甲基，四亚甲基，五亚甲基或3-氧杂三亚甲基; R 6是C 1 -C 18 - 烷基，未取代的或C 1 -C 4 - 烷基 - 或C 1 -C 4 - 烷氧基取代的C 3 -C 8 - 烷基 - 或C 1 -C 4 - 环烷基，C 6 -C 10 - 芳基或C 7 -C 12 - 芳烷基; X 01是-O-或-NH-; T是C连接的C 3 -C 20 - 亚杂芳基; v为0或1至4的整数; 杂亚芳基的杂环中的X 1相对于T-C *键在邻位结合; 和*表示外消旋或对映体纯的非对映异构体或纯外消旋或对映体纯的非对映异构体的混合物。该化合物是金属络合物的优异手性配体，作为用于前手性有机化合物氢化的对映选择性催化剂。

3. 发明申请

WO2005056566A3 METHOD FOR PRODUCING ORTHOMETALATED AND ORTHOSUBSTITUTED AROMATIC COMPOUNDS 审中-公开
标题翻译：制备邻位和正位芳香族化合物的方法
公开(公告)号：WO2005056566A3
公开(公告)日：2005-12-01
申请号：PCT/EP2004053388
申请日：2004-12-10
申请人： SOLVIAS AG , PFALTZ ANDREAS , LOTZ MATTHIAS , SCHOENLEBER MARC , PUGIN BENOIT , KESSELGRUBER MARTIN , THOMMEN MARC
发明人： PFALTZ ANDREAS , LOTZ MATTHIAS , SCHOENLEBER MARC , PUGIN BENOIT , KESSELGRUBER MARTIN , THOMMEN MARC
IPC分类号： C07F9/48 , C07F9/6584 , C07F17/02
CPC分类号： C07F9/65848 , C07F17/02
摘要： The invention relates to compounds having a structural element of formula (I) in an aromatic hydrocarbon ring, wherein: M represents -Li, -MgX3, (C1-C18-Alkyl)3Sn-, -ZnX3 or -B(O-C1-C4-Alkyl)2; X1 and X2, independent of one another, represent O or N, and C-bound hydrocarbon radicals or heterohydrocarbon radicals are bound to the free bonds of the O and N atoms; group -C=C-, together with C atoms, forms a hydrocarbon aromatic compound and represents X3 Cl, Br or I. The inventive compounds are easily obtained by directly substituting the hydrogen in the ortho position to the P atom with metalation reagents. The metal atoms can then be substituted by a reactive electrophilic compound. The group -P(X1-)(X2-)----(BH3)0,1 can then be converted into a secondary phosphine group. The inventive method enables the production of monophosphines and diphosphines even on a large scale, which are valuable ligands for metal complexes serving as catalysts for, e.g. enantioselective hydrogenations.
摘要翻译：具有式（I）的结构元件的化合物中的芳香族烃环，其中M是Li，-MgX3，（C1-C18烷基）3Sn-，-ZnX3或-B（O-C1-C4-烷基）2， X1和X2独立地是O或N-均值和C连接的烃基或杂烃基结合到O和N原子的自由键，形成基团-C = C-的碳一起原子的烃基芳族化合物，和 X3代表Cl，Br或I，通过用金属化试剂将邻位的氢直接取代至P原子而容易地获得。金属原子可以被活性亲电子化合物取代。然后可以将-P（X1-）（X2-） - （BH3）0.1基团转化为仲膦基团。与单 - 和二膦也可以在更大的范围是对于金属配合物作为催化剂用于对映选择性氢化有价值的配体产生的，例如该过程。

4. 发明申请

WO2005108409A2 FERROCENYL LIGANDS FOR HOMOGENEOUS, ENANTIOSELECTIVE HYDROGENATION CATALYSTS 审中-公开
标题翻译：异佛尔酮，选择性氢化催化剂
公开(公告)号：WO2005108409A2
公开(公告)日：2005-11-17
申请号：PCT/EP2005052009
申请日：2005-05-03
申请人： UMICORE AG & CO KG , LOTZ MATTHIAS , SPINDLER FELIX
发明人： LOTZ MATTHIAS , SPINDLER FELIX
IPC分类号： B01J31/22 , C07C51/36 , C07C67/303 , C07C67/31 , C07C213/02 , C07C217/08 , C07C231/18 , C07C233/47 , C07F17/00 , C07F17/02
CPC分类号： C07C231/18 , B01J31/2295 , B01J31/2409 , B01J31/2433 , B01J31/2438 , B01J2231/643 , B01J2231/645 , B01J2531/0286 , B01J2531/821 , B01J2531/822 , B01J2531/827 , C07B2200/07 , C07C51/36 , C07C67/303 , C07C67/31 , C07C213/02 , C07F17/02 , C07C57/30 , C07C69/34 , C07C69/732 , C07C69/675 , C07C217/08 , C07C233/47
摘要： Compounds of the formula (I) or (I'), where R1 is a hydrogen atom or C1-C4-alkyl and R'1 is C1-C4-alkyl; X1 and X2 are each, independently of one another, a secondary phosphine group; R2 is hydrogen, R01R02R03Si-, C1-C18 -acyl substituted by halogen, hydroxy, C1-C8-alkoxy or R04R05N-,-or R06-X01-C(O)-; R01, R02 and R03 are each, independently of one another, C1-C12-alkyl, unsubstituted or C1-C4-alkylor C1-C4-alkoxy-substituted C6-C10-aryl or C7-C12-aralkyl; R04 and R05 are each, independently of one another, hydrogen, C1-C12-alkyl, C3-C8-cycloalkyl, C6-C10-aryl or C7-C12-aralkyl, or R04 and R05 together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; R06 is C1-C18-alkyl, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkyl, C6-C10-aryl or C7-C12-aralkyl; X01 is -O- or -NH-; T is C6-C20-arylene; v is 0 or an integer from 1 to 4; and * denotes a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically diastereomers, are excellent chiral ligands for metal complexes as enantioselective catalysts for the hydrogenation of prochiral organic compounds.
摘要翻译：式（I）或（I'）的化合物，其中R 1是氢原子或C 1 -C 4烷基，R 11是C 1 -C 4 - 烷基; X1和X2各自独立地为次膦基; R2是氢，R01R02R03Si-，被卤素取代的C1-C18-酰基，羟基，C1-C8-烷氧基或R04R05N - ， - 或R06-X01-C（O） - ; R01，R02和R03各自独立地为C1-C12-烷基，未取代的或C1-C4-烷基或C1-C4-烷氧基取代的C6-C10-芳基或C7-C12-芳烷基; R 04和R 05彼此独立地为氢，C 1 -C 12 - 烷基，C 3 -C 8 - 环烷基，C 6 -C 10 - 芳基或C 7 -C 12 - 芳烷基，或R 04和R 05一起是三亚甲基，四亚甲基，五亚甲基或3 -oxapentylene; R06是C 1 -C 18烷基，未取代的或C 1 -C 4烷基 - 或C 1 -C 4 - 烷氧基取代的C 3 -C 8 - 环烷基，C 6 -C 10 - 芳基或C 7 -C 12 - 芳烷基; X01为-O-或-NH-; T是C 6 -C 20亚芳基; v为0或1至4的整数; 和*表示外消旋或对映体纯的非对映异构体或纯外消旋或对映异构体非对映异构体的混合物，作为用于前手性有机化合物氢化的对映选择性催化剂的金属络合物的优异手性配体。

5. 发明专利

CA2662393C PROCESS FOR PREPARING BIARYL SUBSTITUTED 4-AMINO-BUTYRIC ACID OR DERIVATIVES THEREOF AND THEIR USE IN THE PRODUCTION OF NEP INHIBITORS 未知
公开(公告)号：CA2662393C
公开(公告)日：2015-11-03
申请号：CA2662393
申请日：2007-09-11
申请人： NOVARTIS AG
发明人： HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
IPC分类号： C07C227/16 , C07C227/32 , C07C229/34
摘要： The invention relates to a process for producing a compound according to formula (i) or salt thereof, wherein R1 and R1´ are independently hydrogen or an amine protecting group and R2 is a carboxyl group or an ester group, comprising reacting a compound according to formula (ii) or salt thereof, wherein R1, R1´ and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.

6. 发明专利

HK1131381A1 PROCESS FOR PREPARING BIARYL SUBSTITUTED 4-AMINO-BUTYRIC ACID OR DERIVATIVES THEREOF AND THEIR USE IN THE PRODUCTION OF NEP INHIBITORS 4-- NEP 未知
公开(公告)号：HK1131381A1
公开(公告)日：2010-01-22
申请号：HK09111344
申请日：2009-12-03
申请人： NOVARTIS AG
发明人： HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
IPC分类号： C07C20060101
摘要： The invention relates to a process for producing a compound according to formula (i) wherein R1 and R1' are independently hydrogen or an amine protecting group and R2 is a carboxylic group or derivative thereof, comprising reacting a compound according to formula (ii) wherein R1, R1' and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and optionally a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.

7. 发明专利

NO20091242L 未知
公开(公告)号：NO20091242L
公开(公告)日：2009-03-25
申请号：NO20091242
申请日：2009-03-25
申请人： NOVARTIS AG
发明人： WIETFELD BERNHARD , HOOK DAVID , LOTZ MATTHIAS
IPC分类号： C07C227/16 , C07C227/32 , C07C229/34
摘要： The invention relates to a process for producing a compound according to formula (i) wherein R1 and R1' are independently hydrogen or an amine protecting group and R2 is a carboxylic group or derivative thereof, comprising reacting a compound according to formula (ii) wherein R1, R1' and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and optionally a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.

8. 发明专利

NO341967B1 Fremgangsmåte for fremstilling av biarylsubstituerte 4-aminosmørsyre eller derivater derav og deres anvendelse ved fremstilling av NEP-inhibitorer 未知
公开(公告)号：NO341967B1
公开(公告)日：2018-03-05
申请号：NO20091242
申请日：2009-03-25
申请人： NOVARTIS AG
发明人： WIETFELD BERNHARD , HOOK DAVID , LOTZ MATTHIAS
IPC分类号： C07C269/06 , C07C271/22
摘要： Oppfinnelsen angår en fremgangsmåte for fremstilling av en forbindelse med formel (i) (i) eller salt derav, hvori R1 og R1' er uavhengig hydrogen eller en aminbeskyttende gruppe og R2 er en karboksylgruppe eller en estergruppe, som innbefatter omsetning av en forbindelse med formel (ii) (ii) eller salt derav, hvori R1, R1'og R2 er som definert ovenfor, med hydrogen under nærvær av en overgangsmetallkatalysator og en kiral ligand, hvori overgangsmetallet er valgt fra gruppe 7, 8 eller 9 i det periodiske system. Videre angår oppfinnelsen produkter oppnådd ved nevnte fremgangsmåte og deres anvendelse ved fremstilling av NEP-inhibitorer. Videre angår oppfinnelsen anvendelse av overgangsmetallkatalysator ved fremstilling av NEP-inhibitorer eller prodrug derav.

9. 发明专利

HRP20140984T1 POSTUPAK ZA PROIZVODNJU BIARIL-SUPSTITUIRANE 4-AMINO-BUTIRIÄŚNE KISELINE ILI NJEZINIH DERIVATA TE NJIHOVA UPORABA U PROIZVODNJI NEP-INHIBITORA 未知
公开(公告)号：HRP20140984T1
公开(公告)日：2014-12-05
申请号：HRP20140984
申请日：2014-10-14
申请人： NOVARTIS AG
发明人： HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
IPC分类号： C07C227/16 , C07C227/32 , C07C229/34

10. 发明专利

SI2066618T1 Postopek za pripravo biarilno substituirane 4-amino-maslene kisline ali njenih derivatov in njihova uporaba pri izdelavi NEP inhibitorjev 未知
公开(公告)号：SI2066618T1
公开(公告)日：2014-11-28
申请号：SI200731518
申请日：2007-09-11
申请人： NOVARTIS AG
发明人： HOOK DAVID , WIETFELD BERNHARD , LOTZ MATTHIAS
IPC分类号： C07C227/00 , C07C229/00

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