公开(公告)号：EP1015432A1

公开(公告)日：2000-07-05

申请号：EP98944648.9

申请日：1998-09-02

Applicant: B.I. Chemicals, Inc.

Inventor： DEMIAN, Iulia ,  STANLEY, Kenneth, D.

IPC: C07D217/20

CPC classification number: C07D217/20

Abstract: This invention describes a process for the isolation of (-)1-(p-methoxybenzyl)-1, 2,3,4,5,6,7,8- octahydroisoquinoline from a racemic mixture, which involves treating partially resolved mixtures with a formic acid to form a nearly-racemic salt for further resolution.

Abstract translation: 本发明描述了从外消旋混合物中分离（ - ）1-（对甲氧基苄基）-1,2,3,4,5,6,7,8-八氢异喹啉的方法，该方法涉及用 甲酸以形成近乎外消旋的盐用于进一步的拆分。

公开(公告)号：EP0929527A1

公开(公告)日：1999-07-21

申请号：EP97936381.0

申请日：1997-08-04

Applicant: HOECHST MARION ROUSSEL, INC.

Inventor： WATSON, Timothy, James-Norman

IPC: C07D217

CPC classification number: C07D217/20 ,  C07D217/06

Abstract: A commercial scale process for the production of tetrahydroisoquinolines and related heterocyclics by reaction, in mildly acidic conditions, of aryl N-sulfonylethylamines in the presence of suitable Lewis acid, and a compound capable of in situ generation of formaldehyde. The process is further characterized by formaldehyde being generated by the reaction of the Lewis acid upon the formaldehyde generating agent, instead of being present as an initial reactant. The process further avoids the presence of initial water which destroys the Lewis acid before it can act upon the formaldehyde generating agent.

公开(公告)号：EP0315886B1

公开(公告)日：1995-02-15

申请号：EP88118220.8

申请日：1988-11-02

Applicant: F. HOFFMANN-LA ROCHE AG

Inventor： Broger, Emil Albin, Dr. ,  Crameri, Yvo, Dr. ,  Heiser, Bernd, Dr.

IPC: C07D217/20

CPC classification number: C07F15/0053 ,  C07D217/20

公开(公告)号：EP0307168A3

公开(公告)日：1990-07-04

申请号：EP88308235.6

申请日：1988-09-06

Applicant: Takasago International Corporation

Inventor： Sayo, Noboru Takasago Int. Corporation ,  Takemasa, Toshiro Takasago Int. Corporation ,  Kumobayashi, Hidenori Takasago Int. Corporation

IPC: C07F15/00 ,  B01J31/24

CPC classification number: B01J31/2452 ,  B01J2231/645 ,  B01J2531/0219 ,  B01J2531/26 ,  B01J2531/31 ,  B01J2531/42 ,  B01J2531/46 ,  B01J2531/822 ,  C07D217/20 ,  C07F15/0053

Abstract: A ruthenium-phosphine complex having a 2,2′ bis(diphen­ylphosphino)-1,1′ -binapthyl ligand is of the general formula:
[RU(R-BINAP)MCl k ] l X m
wherein R-BlNAP represents a tertiary phosphine represented by the formula:
wherein R represents hydrogen or methyl; M represents Zn, Al, Ti or Sn; X represents N(C₂ H₅)₃ or CH₃CO₂ ; when X represents N(C₂ H ₅)₃, l is 2 and m is 1, and when M repre­sents Zn, k is 4, when M represents Al, k is 5, and when M represents Ti or Sn, k is 6; and when X represents CH₃CO₂ , l is 1 and m is 2, and when M represents Zn, k is 2, when M represents Al, k is 3, and when M represents Ti or Sn, k is 4. 16 specific complexes are exemplified. Synthesis is from Ru₂ Cl₄ (R-BINAP)NC₂ H₅ or Ru(CH₃CO₂)₂ (R-BlNAP), by reaction with the Lewis acid ZnCl ₂, AlCl₃ , TiCl₆ or SnCl to give the desired MCl₃ group at 10-25 °C for 2-20 hours in a solvent, e.g. methylene chloride. Optically active R-BINAP can be used. The complex is an excellent catalyst for asymmetric hydrogenation of enamides with high activity.

公开(公告)号：EP0315886A2

公开(公告)日：1989-05-17

申请号：EP88118220.8

申请日：1988-11-02

Applicant: F. HOFFMANN-LA ROCHE AG

Inventor： Broger, Emil Albin, Dr. ,  Crameri, Yvo, Dr. ,  Heiser, Bernd, Dr.

IPC: C07D217/20

CPC classification number: C07F15/0053 ,  C07D217/20

Abstract: The invention is concerned with novel isoquinoline derivatives of the formula
wherein R¹ is hydrogen, lower alkyl, lower alkoxy, aryl, aryloxy, aryl-lower alkyl or aryl-lower alkoxy and R² is phenyl or substituted phenyl.
These novel isoquinoline derivatives are valuable intermediates in the manufacture of morphinan derivatives.

Abstract translation: 本发明涉及式CHEM的新型异喹啉衍生物，其中R 1是氢，低级烷基，低级烷氧基，芳基，芳氧基，芳基 - 低级烷基或芳基 - 低级烷氧基，R 2是苯基或取代的 苯基。 这些新型异喹啉衍生物是制造吗啡喃衍生物的有价值的中间体。

公开(公告)号：EP0307168A2

公开(公告)日：1989-03-15

申请号：EP88308235.6

申请日：1988-09-06

Applicant: Takasago International Corporation

Inventor： Sayo, Noboru Takasago Int. Corporation ,  Takemasa, Toshiro Takasago Int. Corporation ,  Kumobayashi, Hidenori Takasago Int. Corporation

IPC: C07F15/00 ,  B01J31/24

CPC classification number: B01J31/2452 ,  B01J2231/645 ,  B01J2531/0219 ,  B01J2531/26 ,  B01J2531/31 ,  B01J2531/42 ,  B01J2531/46 ,  B01J2531/822 ,  C07D217/20 ,  C07F15/0053

Abstract: A ruthenium-phosphine complex having a 2,2′ bis(diphen­ylphosphino)-1,1′ -binapthyl ligand is of the general formula:

[RU(R-BINAP)MCl k ] l X m

wherein R-BlNAP represents a tertiary phosphine represented by the formula:
wherein R represents hydrogen or methyl; M represents Zn, Al, Ti or Sn; X represents N(C₂ H₅)₃ or CH₃CO₂ ; when X represents N(C₂ H ₅)₃, l is 2 and m is 1, and when M repre­sents Zn, k is 4, when M represents Al, k is 5, and when M represents Ti or Sn, k is 6; and when X represents CH₃CO₂ , l is 1 and m is 2, and when M represents Zn, k is 2, when M represents Al, k is 3, and when M represents Ti or Sn, k is 4.
16 specific complexes are exemplified. Synthesis is from Ru₂ Cl₄ (R-BINAP)NC₂ H₅ or Ru(CH₃CO₂)₂ (R-BlNAP), by reaction with the Lewis acid ZnCl ₂, AlCl₃ , TiCl₆ or SnCl to give the desired MCl₃ group at 10-25 °C for 2-20 hours in a solvent, e.g. methylene chloride. Optically active R-BINAP can be used.
The complex is an excellent catalyst for asymmetric hydrogenation of enamides with high activity.

Abstract translation: 具有2,2分钟双（二苯基膦基）-1,1min - 双乙基配位体的钌 - 膦配合物具有以下通式：[RU（R-BINAP）MClk] 1Xm其中R-BlNAP代表由 式：其中R表示氢或甲基; M表示Zn，Al，Ti或Sn; X表示N（C 2 H 5）3或CH 3 CO 2; 当X表示N（C2H5）3时，l为2，m为1，当M表示Zn时，k为4，当M表示Al时，k为5，当M表示Ti或Sn时，k为6; 当X表示CH3CO2时，l为1，m为2，当M表示Zn时，k为2，当M表示Al时，k为3，当M表示Ti或Sn时，k为4.16的特定配合物 。 通过与路易斯酸ZnCl 2，AlCl 3，TiCl 6或SnCl反应合成来自Ru 2 Cl 4（R-BINAP）NC 2 H 5或Ru（CH 3 CO 2）2（R-BlNAP），在10-25℃下得到所需的MCl 3基团 在溶剂中2-20小时，例如 二氯甲烷。 可以使用光学活性的R-BINAP。 该复合物是具有高活性的烯酰胺的不对称氢化的优异催化剂。

公开(公告)号：EP0210828A3

公开(公告)日：1988-03-16

申请号：EP86305637

申请日：1986-07-22

Applicant: SMITHKLINE BECKMAN CORPORATION

Inventor： Kaiser, Carl ,  Kruse, Lawrence Ivan

IPC: C07D217/20 ,  A61K31/47

CPC classification number: C07D217/20

Abstract: Compounds of structure (I)
where Y is OH, X₁ is C₁ - ₄alkoxy, X₂ is C₁ - ₄alkoxy, halogen, CF₃ or C₁ - ₄alkyl, processes for their preparation, compositions containing them and their use as β-adrenergic receptor antagonists.

公开(公告)号：EP0219616A1

公开(公告)日：1987-04-29

申请号：EP86110018.8

申请日：1986-07-21

Applicant: S O "PHARMACHIM"

Inventor： Ivanov, Tschavdar Borissov ,  Mondeschka, Diana Minkova ,  Stoev, Georgi Georgiev ,  Mizov, Vladimir Sdravkov ,  Sabunova,, Orhideya Bontscheva ,  Batschvarova, Anna Siderova ,  Todorova, Maria Georgieva ,  Genova, Ani Iavnova ,  Spirova, Neli Stefanova ,  Stoimenov, Georgi Borissov ,  Iliev, Dimiter Pavlov ,  Nissimov, Yossif Nissim ,  Taneva, Nedyalka Ivanova ,  Spirov, Georgi Georgiev ,  Vassileva, Raina Stefanova

IPC: C07D217/20

CPC classification number: C07D217/20

Abstract: Dichlormethylat des N,N-4,10-Dioxa-3,11-dioxotridezylen-1, 13-bis-tetrahydropapaverin der allgemeinen Formel I
sowie ein Verfahren zu seiner Herstellung.

Abstract translation: 通式I的N，N-4,10-二氧杂-3,11-二氧杂三氮杂环庚烯-1,13-双 - 四氢罂粟碱的二氯甲基化物及其制备方法。

公开(公告)号：EP0054309A1

公开(公告)日：1982-06-23

申请号：EP81110513.9

申请日：1981-12-16

Applicant: THE WELLCOME FOUNDATION LIMITED

Inventor： El-Sayad, Hassan Ali ,  Yeowell, David Arthur ,  Swaringen, Roy Archibald, Jr.

IPC: C07D217/20 ,  A61K31/47

CPC classification number: C07D217/20

Abstract: This invention relates to long duration neuromuscular blocking agents, known examples of which agents have been found to have cardiovascular and other side effects, and seeks to overcome the shortcomings of presently used agents. The compounds of this invention are trans, trans-2,2 1 -(dimethylenebis(carbonyloxy- trimethylene))bis(1,2,3,4-tetrahydro-6,7,8-trimethoxy-2-alkyl-1-(3,4,5-trimethoxybenzyl)isoquinolinium salts. A preferred compound has the following structure:

Abstract translation: 本发明涉及长的持续时间神经肌肉阻断剂，已发现哪个剂的已知实例有心血管等副作用，并寻求克服目前使用的试剂的短缺憾。 本发明的化合物是反式，反 - 2,2-二<1> - （dimethylenebis（羰氧基三亚甲基））二（1,2,3,4-四氢-6,7,8-三甲氧基-2-烷基-1- - （3,4,5-三甲氧基苄基）异喹啉盐的优选化合物具有以下结构升。

公开(公告)号：EP2344456B1

公开(公告)日：2018-07-25

申请号：EP09785009.3

申请日：2009-08-27

Applicant: Japan Tobacco Inc.

Inventor： JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  JONES, Simon, Mark ,  POLLARD, Derek, Roland ,  HARTZOULAKIS, Basil ,  PAYNE, Helen ,  MADGE, David ,  FORD, John

IPC: C07D211/08 ,  C07D217/16 ,  C07D231/18 ,  C07D233/84 ,  C07D265/30 ,  C07D277/36 ,  C07D307/64 ,  C07D311/58 ,  C07D333/34 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D295/192 ,  A61K31/18 ,  A61P29/00

CPC classification number: C07D295/18 ,  C07D207/12 ,  C07D211/10 ,  C07D211/16 ,  C07D211/22 ,  C07D211/48 ,  C07D211/52 ,  C07D217/20 ,  C07D231/18 ,  C07D233/84 ,  C07D241/04 ,  C07D265/30 ,  C07D277/36 ,  C07D307/64 ,  C07D311/58 ,  C07D333/34

Abstract: The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives wherein R1, R2, R3, X1, and A are defined herein. The compounds are useful as potassium ion channel inhibitors.