公开(公告)号：US07402587B2

公开(公告)日：2008-07-22

申请号：US11596260

申请日：2005-05-12

申请人： Thierry Briand ,  Alexander Bilz ,  Fritz Blatter ,  Martin Szelagiewicz

发明人： Thierry Briand ,  Alexander Bilz ,  Fritz Blatter ,  Martin Szelagiewicz

IPC分类号： C07D401/14 ,  A61K31/506

CPC分类号： C07D401/14

摘要： Crystalline forms A and B of 5-methyl-pyridine-2-sulfonic acid [6-methoxy-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide of formula (I) are described, whereby form B is the most stable form. 5-methyl-pyridine-2-sulfonic acid [6-methoxy-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-amide also forms solvates with, for example, ethanol, acetone, tetrahydrofuran, methanol, isopropanol, 2-butanone and dichloromethane.

摘要翻译： 式（A）的5-甲基 - 吡啶-2-磺酸[6-甲氧基-5-（2-甲氧基 - 苯氧基）-2-吡啶-4-基 - 嘧啶-4-基] - 酰胺的结晶形式A和B I），其中形式B是最稳定的形式。 5-甲基 - 吡啶-2-磺酸[6-甲氧基-5-（2-甲氧基 - 苯氧基）-2-吡啶-4-基 - 嘧啶-4-基] - 酰胺也与例如乙醇 ，丙酮，四氢呋喃，甲醇，异丙醇，2-丁酮和二氯甲烷。

公开(公告)号：US07153675B2

公开(公告)日：2006-12-26

申请号：US10477739

申请日：2002-04-26

申请人： Peter Herold ,  Stefan Stutz

发明人： Peter Herold ,  Stefan Stutz

IPC分类号： C12P7/62 ,  C12P7/40 ,  C07C69/02

CPC分类号： C12P7/62 ,  C12P41/005

摘要： A process for the preparation of 2(S)-alkyl-5-halogenpent-4-ene carboxylic esters by enzymatic hydrolysis, comprising the steps: a) enzymatic hydrolysis of racemic 2-alkyl-5-halogenpent-4-ene carboxylic esters in aqueous and alkaline medium in the presence of an esterase; b) isolation of 2(S)alkyl-5-halogenpent-4-ene carboxylic esters by extraction with an organic solvent; c) isolation of 2(R)-alkyl-5-halogenpent-4-ene carboxylic acids from the aqueous-alkaline medium; d) Esterification of 2(R)-alkyl-5-halogenpent-4-ene carboxylic acids, e) subsequent racemization to form 2-alkyl-5-halogenpent-4-ene carboxylic esters; and f) return of the racemate obtained in step e) to step a), if necessary together with fresh racemic 2-alkyl-5-halogenpent-4-ene carboxylic esters. The process permits the undesired R-stereoisomers to be converted into the desired 2(S)-alkyl-5-halogenpent-4-ene carboxylic esters to avoid waste product from the synthesis.

摘要翻译： 通过酶水解制备2（S） - 烷基-5-胡椒基-4-戊烯羧酸酯的方法，包括以下步骤：a）将外消旋的2-烷基-5-胡椒基-4-烯羧酸酯酶 水性和碱性介质在酯酶存在下进行; b）通过用有机溶剂萃取分离2（S）烷基-5-胡椒基-4-烯羧酸酯; c）从水性 - 碱性介质中分离2（R） - 烷基-5-胡椒基-4-戊烯羧酸; d）2（R） - 烷基-5-胡椒基-4-烯羧酸的酯化，e）随后的外消旋化以形成2-烷基-5-胡椒戊-4-烯羧酸酯; 和f）如果必要，将步骤e）中获得的外消旋物质与新鲜外消旋的2-烷基-5-胡椒基-4-烯羧酸酯一起返回到步骤a）。 该方法允许将不期望的R-立体异构体转化为所需的2（S） - 烷基-5-胡椒基-4-烯羧酸酯，以避免合成中的废物。

公开(公告)号：US07009078B1

公开(公告)日：2006-03-07

申请号：US10048229

申请日：2000-07-13

申请人： Peter Herold ,  Stefan Stutz ,  Adriano Indolese

发明人： Peter Herold ,  Stefan Stutz ,  Adriano Indolese

IPC分类号： C07C233/04 ,  C07C233/05

CPC分类号： C07D295/185 ,  C07C51/06 ,  C07C57/52 ,  C07C57/76 ,  C07C69/65 ,  C07C231/12 ,  C07C233/09 ,  C07C233/20 ,  C07C235/34 ,  C07C247/12 ,  C07D263/22 ,  C07C237/20

摘要： From compounds of formula II wherein R1 and R2 are independently of one another H, C1–C6alkyl, C1–C6halogenalkyl, C1–C6alkoxy, C1–C6alkoxy-C1–C6alkyl, or C1–C6alkoxy-C1–C6alkyloxy, R3 is C1–C6alkyl, R4 is C1–C6alkyl, and R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6-alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6-alkyl, C1–C6-dialkylamino-C1–C6-alkyl, C1–C6-alkanoylamido-C1–C6-alkyl, HO(O)C—C1–C6-alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2N—C(O)—C1–C6-alkyl, R6 is C1–C6alkyl, R7 is C1–C6alkyl or C1–C6alkoxy, or R6 and R7 together are tetramethylene, pentamethylene, 3-oxa-1,5-pentylene or —CH2CH2O— substituted, if necessary, with C1–C4-Alkyl, phenyl or benzyl, it is possible—through halolactonization, azidation of the halogen group, ring opening with an amine R5—NH2, and reduction of the azide group to form the amino group—to prepare compounds of formula I wherein R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6alkyl, C1–C6dialkylamino-C1–C6-alkyl, C1–C6alkanoylamido-C1–C6alkyl, HO(O)C—C1–C6alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2—N—C(O)—C1–C6alkyl. If 2(S), 7(R)-diastereomer of formula II is used, the 2(S), 4(S), 5(S), 7(S)-diastereomer of formula Ia is obtained in a high degree of purity.

公开(公告)号：US06881868B2

公开(公告)日：2005-04-19

申请号：US10312992

申请日：2001-06-26

申请人： Stefan Stutz ,  Peter Herold ,  Felix Spindler ,  Walter Weissensteiner ,  Thomas Sturm

发明人： Stefan Stutz ,  Peter Herold ,  Felix Spindler ,  Walter Weissensteiner ,  Thomas Sturm

IPC分类号： C07C41/20 ,  C07B61/00 ,  C07C29/147 ,  C07C29/17 ,  C07C43/23 ,  C07C69/734 ,  C07C69/736 ,  C07C41/18

CPC分类号： C07C29/17 ,  C07C29/147 ,  C07C43/23 ,  C07C69/734 ,  C07C33/20 ,  C07C33/30

摘要： Compounds of formula (I), wherein R1 and R2 are, independently of one another, H,C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxyl, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyloxy, and R3 is C1-C6alkyl, are obtainable in high yiedls by stereoselective addition of R3-substituted propionic acid esters to R1- and R2-substituted benzaldehydes of formula R—CHO to form corresponding 3-R-3-hydroxy-2-R3-propionic acid esters, conversion of the OH group to a leaving group, subsequent regioselective elimination to form 3-R-2-R3-propenic acid esters, and reduction to corresponding 3-R-2-R3-allyl alcohols and their enantioselective hydrogenation, wherein R is (a).

摘要翻译： 式（I）化合物，其中R 1和R 2各自独立地为H，C 1 -C 3烷基， C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷氧基，C C 1 -C 6烷氧基-C 1 -C 6烷基或C 1 -C 12 -C 6 -C 6烷氧基-C 1 -C 6烷氧基，R 3是C 1 可以通过立体选择性加成R 3 - 取代的丙酸酯与R 1 - （C 1 -C 6）烷基取代， 和R 2 CHO的R 2取代的苯甲醛形成相应的3-R-3-羟基-2-R 3 - 丙酸酯，OH基团的转化 到离去基团，随后进行区域选择性消除以形成3-R-2-R 3 - 丙酸酯，并还原成相应的3-R-2-R 3 - 烯丙醇及其对映选择性氢化，其中R为（a）。

公开(公告)号：US07132569B2

公开(公告)日：2006-11-07

申请号：US11254749

申请日：2005-10-21

申请人： Peter Herold ,  Stefan Stutz ,  Adriano Indolese

发明人： Peter Herold ,  Stefan Stutz ,  Adriano Indolese

IPC分类号： C07C233/04 ,  C07C233/05

CPC分类号： C07D295/185 ,  C07C51/06 ,  C07C57/52 ,  C07C57/76 ,  C07C69/65 ,  C07C231/12 ,  C07C233/09 ,  C07C233/20 ,  C07C235/34 ,  C07C247/12 ,  C07D263/22 ,  C07C237/20

摘要： From compounds of formula II wherein R1 and R2 are independently of one another H, C1–C6alkyl, C1–C6halogenalkyl, C1–C6alkoxy, C1–C6alkoxy-C1–C6alkyl, or C1–C6alkoxy-C1–C6alkyloxy, R3 is C1–C6alkyl, R4 is C1–C6alkyl, and R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6-alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6-alkyl, C1–C6-dialkylamino-C1–C6-alkyl, C1–C6-alkanoylamido-C1–C6-alkyl, HO(O)C—C1–C6-alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2N—C(O)—C1–C6-alkyl, R6 is C1–C6alkyl, R7 is C1–C6alkyl or C1–C6alkoxy, or R6 and R7 together are tetramethylene, pentamethylene, 3-oxa-1,5-pentylene or —CH2CH2O— substituted, if necessary, with C1–C4-Alkyl, phenyl or benzyl, it is possible—through halolactonization, azidation of the halogen group, ring opening with an amine R5—NH2, and reduction of the azide group to form the amino group—to prepare compounds of formula I wherein R5 is C1–C6alkyl, C1–C6hydroxyalkyl, C1–C6alkoxy-C1–C6alkyl, C1–C6alkanoyloxy-C1–C6alkyl, C1–C6aminoalkyl, C1–C6alkylamino-C1–C6alkyl, C1–C6dialkylamino-C1–C6-alkyl, C1–C6alkanoylamido-C1–C6alkyl, HO(O)C—C1–C6alkyl, C1–C6alkyl-O—(O)C—C1–C6alkyl, H2N—C(O)—C1–C6alkyl, C1–C6alkyl-HN—C(O)—C1–C6alkyl or (C1–C6alkyl)2—N—C(O)—C1–C6alkyl. If 2(S),7(R)-diastereomer of formula II is used, the 2(S),4(S),5(S),7(S)-diastereomer of formula Ia is obtained in a high degree of purity.