公开(公告)号：WO1995011224A1

公开(公告)日：1995-04-27

申请号：PCT/US1994010852

申请日：1994-09-26

Applicant: ABBOTT LABORATORIES

Inventor： ABBOTT LABORATORIES ,  STUK, Timothy, L. ,  KERDESKY, Francis, A., J. ,  LIJEWSKI, Linda, M. ,  NORBECK, Daniel, W. ,  SCARPETTI, David ,  TIEN, Jien-Heh, J. ,  ALLEN, Michael, S. ,  LANGRIDGE, Denton, C. ,  MELCHER, Laura ,  RENO, Daniel, S. ,  SHAM, Hing, Leung ,  ZHAO, Chen ,  HAIGHT, Anthony, R. ,  LEANNA, M., Robert ,  MORTON, Howard, E. ,  ROBBINS, Timothy, A. ,  SOWIN, Thomas, J.

IPC: C07C225/16

CPC classification number: C07D221/14 ,  C07B2200/07 ,  C07C213/00 ,  C07C215/28 ,  C07C225/16 ,  C07C251/40 ,  C07C255/42 ,  C07C269/06 ,  C07C271/20 ,  C07D209/44 ,  C07C215/08

Abstract: Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of formula (3), wherein R6 and R7 are each hydrogen or R6 and R7 are independently selected from (i), wherein Ra and Rb are independently selected from hydrogen, loweralkyl and phenyl and Rc, Rd and Re are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and (ii) wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or R6 is as defined above and R7 is R7aOC (O)-wherein R7a is loweralkyl or benzyl; or R6 and R7 taken together with the nitrogen atom to which they are bonded are (a) or (b), wherein Rf, Rg, Rh and Ri are independently selected from hydrogen, loweralkyl, alkoxy, halogen and trifluoromethyl and R8 is hydrogen or -C(O)R" wherein R" is loweralkyl, alkoxy, benzyloxy or phenyl wherein the phenyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or an acid addition salt thereof.

Abstract translation: 公开了可用于制备基本上纯的式（3）化合物的中间体和方法，其中R 6和R 7各自为氢或R 6和R 7独立地选自（ⅰ），其中R a和R b独立地选自氢 ，低级烷基和苯基，Rc，Rd和Re独立地选自氢，低级烷基，三氟甲基，烷氧基，卤素和苯基; 和（ii）其中萘基环是未取代的或被一个，两个或三个独立地选自低级烷基，三氟甲基，烷氧基和卤素的取代基取代; 或R 6如上所定义，且R 7为R 7 a OC（O） - 其中R 7a为低级烷基或苄基; 或R 6和R 7与它们所键合的氮原子一起是（a）或（b），其中R f，R g，Rh和R 1独立地选自氢，低级烷基，烷氧基，卤素和三氟甲基，并且R 8是氢或 -C（O）R“其中R”是低级烷基，烷氧基，苄氧基或苯基，其中苯环是未取代的或被一个，两个或三个独立地选自低级烷基，三氟甲基，烷氧基和卤素的取代基取代; 或其酸加成盐。

公开(公告)号：EP0984921B1

公开(公告)日：2002-09-18

申请号：EP98923656.7

申请日：1998-05-19

Applicant: Abbott Laboratories

Inventor： HAIGHT, Anthony, R. ,  STUK, Timothy, L. ,  MENZIA, Jerome, A.

IPC: C07C221/00 ,  C07C225/16

CPC classification number: C07C221/00 ,  C07C225/16

Abstract: The present invention discloses a process for the preparation of a substantially pure compound having formula (4). The process comprises the step of reacting an enolate having formula (A) with a Grignard reagent. The enolate salt is formed in situ from the reaction of a protected ester wherein M is an alkali metal. R6 and R7 are each hydrogen or are independently selected from (i) wherein Ra and Rb are independently selected from hydrogen, lower alkyl and phenyl and Rc, Rd and Re are independently selected from hydrogen, lower alkyl, trifluoromethyl, alkoxy, halo and phenyl; and (ii) wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from lower alkyl, trifluoromethyl, alkoxy and halo. Alternatively, R6 is as defined above and R7 is R12OC(O)- wherein R12 is benzyl; or R6 and R7 taken together with the nitrogen atom to which they are bonded form (B) or (C), wherein Rf, Rg, Rh and Ri are independently selected from hydrogen, lower alkyl, alkoxy, halogen and trifluoromethyl.

公开(公告)号：EP0984921A1

公开(公告)日：2000-03-15

申请号：EP98923656.7

申请日：1998-05-19

Applicant: Abbott Laboratories

Inventor： HAIGHT, Anthony, R. ,  STUK, Timothy, L. ,  MENZIA, Jerome, A.

IPC: C07C221/00 ,  C07C225/16

CPC classification number: C07C221/00 ,  C07C225/16

Abstract: The present invention discloses a process for the preparation of a substantially pure compound having formula (4). The process comprises the step of reacting an enolate having formula (A) with a Grignard reagent. The enolate salt is formed in situ from the reaction of a protected ester wherein M is an alkali metal. R6 and R7 are each hydrogen or are independently selected from (i) wherein Ra and Rb are independently selected from hydrogen, lower alkyl and phenyl and Rc, Rd and Re are independently selected from hydrogen, lower alkyl, trifluoromethyl, alkoxy, halo and phenyl; and (ii) wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from lower alkyl, trifluoromethyl, alkoxy and halo. Alternatively, R6 is as defined above and R7 is R12OC(O)- wherein R12 is benzyl; or R6 and R7 taken together with the nitrogen atom to which they are bonded form (B) or (C), wherein Rf, Rg, Rh and Ri are independently selected from hydrogen, lower alkyl, alkoxy, halogen and trifluoromethyl.

公开(公告)号：EP0724563B1

公开(公告)日：1999-09-01

申请号：EP94929340.1

申请日：1994-09-26

Applicant: ABBOTT LABORATORIES

Inventor： STUK, Timothy, L. ,  KERDESKY, Francis, A., J. ,  LIJEWSKI, Linda, M. ,  NORBECK, Daniel, W. ,  SCARPETTI, David ,  TIEN, Jien-Heh, J. ,  ALLEN, Michael, S. ,  LANGRIDGE, Denton, C. ,  MELCHER, Laura ,  RENO, Daniel, S. ,  SHAM, Hing, Leung ,  ZHAO, Chen ,  HAIGHT, Anthony, R. ,  LEANNA, M., Robert ,  MORTON, Howard, E. ,  ROBBINS, Timothy, A. ,  SOWIN, Thomas, J.

IPC: C07C225/16 ,  C07C213/00 ,  C07C255/42 ,  C07C271/20 ,  C07C269/06 ,  C07C215/28 ,  C07C251/40

CPC classification number: C07D221/14 ,  C07B2200/07 ,  C07C213/00 ,  C07C215/28 ,  C07C225/16 ,  C07C251/40 ,  C07C255/42 ,  C07C269/06 ,  C07C271/20 ,  C07D209/44 ,  C07C215/08

Abstract: Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of formula (3), wherein R6 and R7 are each hydrogen or R6 and R7 are independently selected from (i), wherein Ra and Rb are independently selected from hydrogen, loweralkyl and phenyl and Rc, Rd and Re are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and (ii) wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or R6 is as defined above and R7 is R7aOC (O)-wherein R7a is loweralkyl or benzyl; or R6 and R7 taken together with the nitrogen atom to which they are bonded are (a) or (b), wherein Rf, Rg, Rh and Ri are independently selected from hydrogen, loweralkyl, alkoxy, halogen and trifluoromethyl and R8 is hydrogen or -C(O)R' wherein R' is loweralkyl, alkoxy, benzyloxy or phenyl wherein the phenyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or an acid addition salt thereof.

公开(公告)号：EP0724563A1

公开(公告)日：1996-08-07

申请号：EP94929340.0

申请日：1994-09-26

Applicant: ABBOTT LABORATORIES

Inventor： STUK, Timothy, L. ,  KERDESKY, Francis, A., J. ,  LIJEWSKI, Linda, M. ,  NORBECK, Daniel, W. ,  SCARPETTI, David ,  TIEN, Jien-Heh, J. ,  ALLEN, Michael, S. ,  LANGRIDGE, Denton, C. ,  MELCHER, Laura ,  RENO, Daniel, S. ,  SHAM, Hing, Leung ,  ZHAO, Chen ,  HAIGHT, Anthony, R. ,  LEANNA, M., Robert ,  MORTON, Howard, E. ,  ROBBINS, Timothy, A. ,  SOWIN, Thomas, J.

IPC: C07C213 ,  C07C215 ,  C07C225 ,  C07C227 ,  C07C229 ,  C07C231 ,  C07C233 ,  C07C251 ,  C07C255 ,  C07C269 ,  C07C271 ,  C07D209 ,  C07D221

CPC classification number: C07D221/14 ,  C07B2200/07 ,  C07C213/00 ,  C07C215/28 ,  C07C225/16 ,  C07C251/40 ,  C07C255/42 ,  C07C269/06 ,  C07C271/20 ,  C07D209/44 ,  C07C215/08

Abstract: Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of formula (3), wherein R6 and R7 are each hydrogen or R6 and R7 are independently selected from (i), wherein Ra and Rb are independently selected from hydrogen, loweralkyl and phenyl and Rc, Rd and Re are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and (ii) wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or R6 is as defined above and R7 is R7aOC (O)-wherein R7a is loweralkyl or benzyl; or R6 and R7 taken together with the nitrogen atom to which they are bonded are (a) or (b), wherein Rf, Rg, Rh and Ri are independently selected from hydrogen, loweralkyl, alkoxy, halogen and trifluoromethyl and R8 is hydrogen or -C(O)R' wherein R' is loweralkyl, alkoxy, benzyloxy or phenyl wherein the phenyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or an acid addition salt thereof.