公开(公告)号：WO2011038172A1

公开(公告)日：2011-03-31

申请号：PCT/US2010/050096

申请日：2010-09-24

Applicant: MALLINCKRODT INC. ,  GROTE, Christopher, W. ,  MOSER, Frank, W. ,  WANG, Peter, X. ,  CANTRELL, Gary, L. ,  BERBERICH, David, W.

Inventor： GROTE, Christopher, W. ,  MOSER, Frank, W. ,  WANG, Peter, X. ,  CANTRELL, Gary, L. ,  BERBERICH, David, W.

IPC: C07D217/20

CPC classification number: C07D217/20

Abstract: The present invention provides an efficient process for the preparation of hexahydroisoquinolines from dihydroisoquinolines. In particular, the invention provides a good yielding, one-pot process for the synthesis of hexahydroisoquinolines.

Abstract translation: 本发明提供了一种从二氢异喹啉制备六氢异喹啉的有效方法。 特别地，本发明提供了合成六氢异喹啉的良好产率的一锅法。

公开(公告)号：WO2010096790A1

公开(公告)日：2010-08-26

申请号：PCT/US2010/024963

申请日：2010-02-23

Applicant: MALLINCKRODT INC. ,  CANTRELL, Gary, L. ,  WANG, Peter, X. ,  TRAWICK, Bobby, N. ,  GROTE, Christopher, W. ,  BERBERICH, David, W. ,  SUN, Hang ,  LIAO, Subo

Inventor： CANTRELL, Gary, L. ,  WANG, Peter, X. ,  TRAWICK, Bobby, N. ,  GROTE, Christopher, W. ,  BERBERICH, David, W. ,  SUN, Hang ,  LIAO, Subo

IPC: C07D489/02 ,  A61K31/439 ,  A61P35/00

CPC classification number: C07D489/02

Abstract: The present invention provides (+)-morphinanium N-oxide compounds or pharmaceutically acceptable salts thereof. The invention also provides processes for producing (+)-morphinanium N-oxides or pharmaceutically acceptable salts thereof from the corresponding tertiary N-substituted (+)-morphinan compound or pharmaceutically acceptable salt thereof.

Abstract translation: 本发明提供（+） - 吗啉N-氧化物或其药学上可接受的盐。 本发明还提供了从相应的叔取代（+） - 吗啡喃化合物或其药学上可接受的盐生产（+） - 吗啉N-氧化物或其药学上可接受的盐的方法。

公开(公告)号：WO2009146288A1

公开(公告)日：2009-12-03

申请号：PCT/US2009/044809

申请日：2009-05-21

Applicant: MALLINCKRODT INC. ,  WANG, Peter, X. ,  MOSER, Frank, W. ,  CANTRELL, Gary, L. ,  JIANG, Tao ,  HALVACHS, Robert, E. ,  GROTE, Christopher, W.

Inventor： WANG, Peter, X. ,  MOSER, Frank, W. ,  CANTRELL, Gary, L. ,  JIANG, Tao ,  HALVACHS, Robert, E. ,  GROTE, Christopher, W.

IPC: C07D221/28 ,  C07D489/02 ,  C07D489/08 ,  A61K31/485 ,  A61P29/00 ,  A61P25/00

CPC classification number: C07D489/02 ,  C07D221/28 ,  C07D489/08

Abstract: The invention generally provides processes and intermediate compounds useful for the production of normorphinans and derivatives of normorphinans,eg.

Abstract translation: 本发明通常提供可用于生产正丝菌素和正大脑啡肽衍生物的方法和中间体化合物，例如。

公开(公告)号：WO2009078988A1

公开(公告)日：2009-06-25

申请号：PCT/US2008/013777

申请日：2008-12-17

Applicant: MALLINCKRODT INC. ,  WANG, Peter, X. ,  JIANG, Tao ,  CANTRELL, Gary, L. ,  BERBERICH, David, W. ,  TRAWICK, Bobby, N. ,  LIAO, Subo ,  BRANDT, John

Inventor： WANG, Peter, X. ,  JIANG, Tao ,  CANTRELL, Gary, L. ,  BERBERICH, David, W. ,  TRAWICK, Bobby, N. ,  LIAO, Subo ,  BRANDT, John

IPC: C07D221/28 ,  C07D489/02 ,  A61K31/485

CPC classification number: C07D221/28 ,  C07D489/02

Abstract: The invention generally provides processes and intermediate compounds useful for the production of sinomenine derivatives. In particular, the process may encompass synthetic routes for the production of (+)-sinomenine derivatives and their intermediates.

Abstract translation: 本发明通常提供可用于生产青藤碱衍生物的方法和中间体化合物。 特别地，该方法可以包括用于生产（+） - 青藤碱衍生物及其中间体的合成路线。

公开(公告)号：WO2008130553A1

公开(公告)日：2008-10-30

申请号：PCT/US2008/004869

申请日：2008-04-15

Applicant: MALLINCKRODT INC. ,  WANG, Peter, X. ,  JIANG, Tao ,  CANTRELL, Gary, L. ,  BERBERICH, David, Wayne

Inventor： WANG, Peter, X. ,  JIANG, Tao ,  CANTRELL, Gary, L. ,  BERBERICH, David, Wayne

IPC: C07D489/02 ,  C07D489/08

CPC classification number: C07D489/08 ,  C07D489/02

Abstract: An improved opiate synthesis scheme is provided. An improvement to the oxidation of oripavine and oripavine derivatives comprises the in-situ formation of the peroxacids required to oxidize the oripavine and oripavine derivatives to form an intermediate. An improvement to the reduction of the intermediate to form oxycodone and oxycodone derivatives comprises reduction utilizing a hydrogen transfer reagent. These improvements allow the production of oxycodone and oxycodone derivatives without isolation of the intermediate, providing a one-pot synthesis method.

Abstract translation: 提供了改进的鸦片剂合成方案。 对于oripavine和oripavine衍生物的氧化的改进包括原位形成氧化oripavine和oripavine衍生物以形成中间体所需的过氧酸。 中间体的还原形成羟考酮和羟考酮衍生物的改进包括利用氢转移试剂的还原。 这些改进允许生产羟考酮和羟考酮衍生物而不分离中间体，提供一锅合成方法。

公开(公告)号：WO2008109156A2

公开(公告)日：2008-09-12

申请号：PCT/US2008003070

申请日：2008-03-06

Applicant: MALLINCKRODT INC ,  CANTRELL GARY L ,  WANG PETER X ,  HALVACHS ROBERT E ,  ROESCH KEVIN R ,  BUEHLER HENRY J ,  HAAR JOSEPH P

Inventor： WANG PETER X ,  HALVACHS ROBERT E ,  ROESCH KEVIN R ,  BUEHLER HENRY J ,  HAAR JOSEPH P

CPC classification number: C07D489/08 ,  C07D489/02 ,  C07D489/04 ,  Y02P20/582

Abstract: An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

Abstract translation: 用于叔吗啡喃生物碱碱的N-烷基化以形成相应的季铵盐型吗啡喃生物碱衍生物的改进方法。

公开(公告)号：WO2008073389A3

公开(公告)日：2008-06-19

申请号：PCT/US2007/025262

申请日：2007-12-10

Applicant: MALLINCKRODT INC. ,  WANG, Peter, X. ,  CANTRELL, Gary, L. ,  MAGPARANGALAN, Dan, P. ,  MOSER, Frank, W. ,  BAO, Jian ,  GROTE, Christopher, W.

Inventor： WANG, Peter, X. ,  CANTRELL, Gary, L. ,  MAGPARANGALAN, Dan, P. ,  MOSER, Frank, W. ,  BAO, Jian ,  GROTE, Christopher, W.

IPC: C07D217/02

Abstract: The present invention is directed to processes for the synthesis of morphinans. In particular, a process for the asymmetric reduction of an imine moiety in a 3,4-dihydroisoquinoline to produce a tetrahydroisoquinoline, followed by a Birch reduction to produce a hexahydroisoquinoline. In various embodiments, the 3,4-dihydroisoquinoline contains a phenol moiety protected with a labile protecting group. In other embodiments, the imine reduction reaction mixture contains silver tetrafluoroborate.

公开(公告)号：WO2011038169A3

公开(公告)日：2011-05-19

申请号：PCT/US2010050093

申请日：2010-09-24

Applicant: MALLINCKRODT INC ,  GROTE CHRISTOPHER W ,  MOSER FRANK W ,  WANG PETER X ,  CANTRELL GARY L ,  BERBERICH DAVID W

Inventor： GROTE CHRISTOPHER W ,  MOSER FRANK W ,  WANG PETER X ,  CANTRELL GARY L ,  BERBERICH DAVID W

IPC: C07D217/20

CPC classification number: C07D217/20

Abstract: The present invention provides an efficient process for the preparation of hexahydroisoquinolines from amides. In particular, the invention provides a good yielding, one-pot process for the synthesis of hexahydroisoquinolines.

Abstract translation: 本发明提供了一种从酰胺制备六氢异喹啉的有效方法。 特别地，本发明提供了合成六氢异喹啉的良好产率的一锅法。

公开(公告)号：WO2011038169A2

公开(公告)日：2011-03-31

申请号：PCT/US2010/050093

申请日：2010-09-24

Applicant: MALLINCKRODT INC. ,  GROTE, Christopher, W. ,  MOSER, Frank, W. ,  WANG, Peter, X. ,  CANTRELL, Gary, L. ,  BERBERICH, David, W.

Inventor： GROTE, Christopher, W. ,  MOSER, Frank, W. ,  WANG, Peter, X. ,  CANTRELL, Gary, L. ,  BERBERICH, David, W.

IPC: C07D217/20

CPC classification number: C07D217/20

Abstract: The present invention provides an efficient process for the preparation of hexahydroisoquinolines from amides. In particular, the invention provides a good yielding, one-pot process for the synthesis of hexahydroisoquinolines.

Abstract translation: 本发明提供了一种从酰胺制备六氢异喹啉的有效方法。 特别地，本发明提供了合成六氢异喹啉的良好产率的一锅法。

公开(公告)号：WO2011008636A1

公开(公告)日：2011-01-20

申请号：PCT/US2010/041448

申请日：2010-07-09

Applicant: MALLINCKRODT INC. ,  CANTRELL, Gary L. ,  HALVACHS, Robert E. ,  MOSER, Frank W. ,  BERBERICH, David W. ,  WANG, Peter X.

Inventor： CANTRELL, Gary L. ,  HALVACHS, Robert E. ,  MOSER, Frank W. ,  BERBERICH, David W. ,  WANG, Peter X.

IPC: C07D489/02 ,  A61K31/485 ,  A61P25/04 ,  A61P11/14

CPC classification number: C07D489/02

Abstract: The present invention provides 3-oxy-hydromorphone derivatives, and in particular, 3-ester, 3-carbonate, and 3-sulfonate derivatives of hydromorphone.

Abstract translation: 本发明提供3-羟基 - 氢吗啡酮衍生物，特别是氢吗啡酮的3-酯，3-碳酸酯和3-磺酸酯衍生物。