公开(公告)号：WO03050063A2

公开(公告)日：2003-06-19

申请号：PCT/US0238119

申请日：2002-11-26

申请人： WYETH CORP

发明人： KREFT ANTHONY FRANK ,  ANTANE MADELENE MIYOKO ,  COLE DEREK CECIL ,  KUBRAK DENNIS MARTIN ,  RESNICK LYNN ,  STOCK JOSEPH RAYMOND ,  WANG ZHENG

IPC分类号： A61K31/381 ,  C07B53/00 ,  C07B61/00 ,  C07C209/00 ,  C07C213/00 ,  C07C215/08 ,  C07C227/04 ,  C07C229/08 ,  C07C247/12 ,  C07D227/12 ,  C07D263/26 ,  C07D333/32 ,  C07D333/34 ,  C07C

CPC分类号： C07C215/20 ,  C07B2200/07 ,  C07C215/08 ,  C07C215/24 ,  C07C215/28 ,  C07C215/56 ,  C07C229/08 ,  C07C229/28 ,  C07C229/30 ,  C07C229/36 ,  C07C247/12 ,  C07C323/63 ,  C07D263/26 ,  C07D333/34

摘要： A process is provided for preparing chirally pure S-enantiomers of alpha -amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the Formula (R)2CH(CH2)nCH2X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an alpha -azido acid; h) reducing the alpha -azido acid to the alpha -amino acid; and i) recrystallizing the alpha -amino acid to the chirally pure alpha -amino acid. A process is also provided for preparing chirally pure S-enantiomers of beta -amino alcohols further comprising the steps of reducing the crude alpha -amino acid to the beta -amino alcohol and recrystallizing the beta -amino alcohol to the chirally pure beta -amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl beta -amino alcohols further comprising the steps of sulfonylating the beta -amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl beta -amino alcohols.

摘要翻译： 提供了制备α-氨基酸的手性纯的S-对映异构体的方法，包括以下步骤：a）由式（R）2CH（CH 2）n CH 2 X的烷基卤制备有机金属试剂; b）将有机金属试剂加入到二氧化碳中，得到羧酸; c）在叔胺碱存在下用酰氯，三氯化磷，酸酐或亚硫酰氯活化羧酸; d）使步骤c）的产物与S-4-苄基-2-恶唑烷酮的碱金属盐反应; e）用强非亲核碱处理步骤d）的产物以形成烯醇化物阴离子; f）用2,4,6-三异丙基苯磺酰叠氮化物捕获烯醇化阴离子，得到恶唑烷酮叠氮化物; g）用碱水溶液水解恶唑烷酮叠氮化物，得​​到α-叠氮酸; h）将α-叠氮酸还原成α-氨基酸; 和i）将α-氨基酸重结晶到手性纯的α-氨基酸。 还提供了制备β-氨基醇的手性纯的S-对映异构体的方法，该方法还包括将α-氨基酸粗制还原成β-氨基醇并将β-氨基醇重结晶至手性纯的β-氨基醇 。 还提供了制备N-磺酰基β-氨基醇的手性纯S对映异构体的方法，其还包括用5-氯 - 噻吩-2-磺酰卤磺酰化β-氨基醇的步骤; 并重结晶得到手性纯的N-磺酰基β-氨基醇。

公开(公告)号：WO0242304A3

公开(公告)日：2002-08-29

申请号：PCT/US0145792

申请日：2001-11-01

申请人： WYETH CORP

发明人： SABB ANNMARIE LOUISE ,  VOGEL ROBERT LEWIS ,  NELSON JAMES ALBERT ,  ROSENZWEIG-LIPSON SHARON JOY ,  WELMAKER GREGORY SCOTT ,  SABALSKI JOAN EILEEN ,  SMITH MICHAEL DAVID ,  CHAN ANITA WAI-YIN ,  ANTANE MADELENE MIYOKO ,  RAVEENDRANATH PANOLIL ,  MEGATI SREENIVASULU

IPC分类号： C07D209/94 ,  C07D487/00 ,  C07D487/06 ,  A61K31/551 ,  A61P3/10

CPC分类号： C07D487/06 ,  C07D209/94

摘要： This invention provides compounds of the formulae: (I) or (II), wherein: R1 is hydrogen, alkyl of 1-6 carbon atoms, atoms, acyl of 2-7 carbon atoms, aryl, heteroaryl, or -C(O)R' wherein R' is alkyl of from 1 to 6 carbon atoms, aryl, or heteoaryl; R2 and R3 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, alkoxy of 1-6 carbon atoms, -CH2OH, fluoroalkyl, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, R4 and R5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluoroalkyl, -CN, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluoroalkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, or aroyl; R6 and R7 are each independently hydrogen, C1-C6 alkyl or cycloalkyl; or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions containing these compounds and methods for their use, including treatment of obsessive-compulsive disorder, panic disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, migraine, sleep disorders, eating disorders, obesity, epilepsy, and spinal cord injury.

摘要翻译： 本发明提供式（I）或（II）化合物，其中：R 1是氢，1-6个碳原子的烷基，2-7个碳原子的酰基，芳基，杂芳基或-C（O） R'其中R'是1至6个碳原子的烷基，芳基或杂芳基; R2和R3各自独立地为氢，1-6个碳原子的烷基，3-7个碳原子的环烷基，1-6个碳原子的烷氧基，-CH2OH，氟代烷基，1-6个碳原子的烷基磺酰胺，烷基酰胺 1-6个碳原子的氨基，1-6个碳原子的烷基氨基，每个烷基部分1-6个碳原子的二烷基氨基，R4和R5各自独立地为氢，1-6个碳原子的烷基，1- 6个碳原子，卤素，氟烷基，-CN，1-6个碳原子的烷基磺酰胺，1-6个碳原子的烷基酰胺，1-6个碳原子的烷基氨基，每个烷基部分1-6个碳原子的二烷基氨基， 1-6个碳原子的氟烷氧基，2-7个碳原子的酰基，或芳酰基; R6和R7各自独立地为氢，C1-C6烷基或环烷基; 或其药学上可接受的盐，以及含有这些化合物的药物组合物及其使用方法，包括治疗强迫症，恐慌症，抑郁症，焦虑症，广泛性焦虑症，精神分裂症，偏头痛，睡眠障碍，进食障碍， 肥胖，癫痫和脊髓损伤。