HRP20100040T1 - Postupak dobivanja inhibitora triptaze - Google Patents

Postupak dobivanja inhibitora triptaze Download PDF

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HRP20100040T1
HRP20100040T1 HR20100040T HRP20100040T HRP20100040T1 HR P20100040 T1 HRP20100040 T1 HR P20100040T1 HR 20100040 T HR20100040 T HR 20100040T HR P20100040 T HRP20100040 T HR P20100040T HR P20100040 T1 HRP20100040 T1 HR P20100040T1
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formula
amino
compound
tert
salt
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HR20100040T
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Graf Claus-Dieter
Tappertzhofen Christoph
W Sledeski Adam
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Aventis Pharmaceuticals Inc.
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Priority claimed from EP04004799A external-priority patent/EP1571150A1/en
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract

Postupak dobivanja spoja formule I,gdjeR1 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; iR2 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, 5- do 10- člani heteroaril, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, 5- do 10- člani heteroariloksi, koji sadrži 1, 2, ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, di((C1-C8)-alkil)amino, di-((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; ili njegove soli, naznačen time što se sastoji ua) obradi feniletinilsilanskog spoja formule II, ,gdje G je trimetilsilil, trietilsilil, triizopropilsilil ili dimetil-tert-butilsilil, a R2' je R2, kao što je definirano gore, ili je njegov zaštićeni derivat ili njegov predostatak, u otapalu, hidroksidom, karbonatom ili alkoholatom alkalnog metala ili alkoholatom zemnoalkalnog metala, kako bi se dobilo otopinu feniletina formule III; ib) miješanju dobivene otopine feniletina sa spojem formule IV,gdje X je brom ili jod, R1' je R1, kao što je definirano gore, ili je njegov zaštićeni derivat ili njegov predostatak, a Boc je tert-butoksikarbonil, u prisutnosti homogenog paladijskog katalizatora, kupro soli, te ometanog amina, u otapalu, kako bi se dobilo zaštićeni spoj formule V, ,gdje R1' i R2' su R1 odnosno R2, kao što je definirano gore, ili su njegov zaštićeni derivat ili njegov predostatak, a Boc je tert-butoksikarbonil, ili njegova sol. Patent sadrži još 35 patentnih zahtjeva.

Claims (36)

1. Postupak dobivanja spoja formule I [image] , gdje R1 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; i R2 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, 5- do 10- člani heteroaril, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, 5- do 10- člani heteroariloksi, koji sadrži 1, 2, ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, di((C1-C8)-alkil)amino, di-((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; ili njegove soli, naznačen time što se sastoji u a) obradi feniletinilsilanskog spoja formule II, [image] , gdje G je trimetilsilil, trietilsilil, triizopropilsilil ili dimetil-tert-butilsilil, a R2' je R2, kao što je definirano gore, ili je njegov zaštićeni derivat ili njegov predostatak, u otapalu, hidroksidom, karbonatom ili alkoholatom alkalnog metala ili alkoholatom zemnoalkalnog metala, kako bi se dobilo otopinu feniletina formule III [image] ; i b) miješanju dobivene otopine feniletina sa spojem formule IV [image] , gdje X je brom ili jod, R1' je R1, kao što je definirano gore, ili je njegov zaštićeni derivat ili njegov predostatak, a Boc je tert-butoksikarbonil, u prisutnosti homogenog paladijskog katalizatora, kupro soli, te ometanog amina, u otapalu, kako bi se dobilo zaštićeni spoj formule V, [image] , gdje R1' i R2' su R1 odnosno R2, kao što je definirano gore, ili su njegov zaštićeni derivat ili njegov predostatak, a Boc je tert-butoksikarbonil, ili njegova sol.
2. Postupak, u skladu s patentnim zahtjevom, 1 dobivanja 4-[3-(aminometil)fenil]-1-[5-(2-fluorfeniletinil)-2-furanoil]piperidina formule Ia [image] , ili njegove soli, naznačen time što se sastoji u a) obradi (2-fluorfeniletinil)silil spoj formule IIa [image] , gdje G je trimetilsilil, trietilsilil, triizopropilsilil ili dimetil-tert-butilsilil, u otapalu, hidroksidom, karbonatom ili alkoholatom alkalnog metala ili alkoholatom zemnoalkalnog metala kako bi se dobilo otopinu 2-fluorfeniletina; i b) miješanju dobivene otopine 2-fluorfeniletina sa spojem formule IVa [image] , gdje X je brom ili jod, i Boc je tert-butoksikarbonil, u prisutnosti homogenog paladijskog katalizatora, kupro soli, te ometanog amina, u otapalu, kako bi se dobilo 4-[3-(tert-butoksikarbonilaminometil)fenil]-1-[5-(2-fluorfeniletinil)-2-furanoil]piperidin formule Va [image] , gdje Boc je tert-butoksikarbonil.
3. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time što G je trimetilsilil.
4. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što X je brom.
5. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što se dodatno sastoji u uklanjanju tert-butoksikarbonilne skupine i drugih zaštitnih skupina i/ili prevođenju predostataka prisutnih u spoju formule V ili Va kako bi se dobilo spoj formule I ili Ia, ili njegovu sol.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što se dodatno sastoji u uklanjanju tert-butoksikarbonilne skupine iz spoja formule V ili Va, u prisutnosti kiseline, kako bi se dobilo spoj formule I ili Ia, ili njegovu sol.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što se dodatno sastoji u uklanjanju tert-butoksikarbonilne skupine iz 4-[3-(tert-butoksikarbonilaminometil)fenil]-1-[5-(2-fluorfeniletinil)-2-furanoil]piperidina, u prisutnosti metansulfonske kiseline, kako bi se dobilo sol 4-[3-(aminometil)fenil]-1-[5-(2-fluorfeniletinil)-2-furanoil]piperidina s metansulfonskom kiselinom.
8. Postupak dobivanja spoja formule IV [image] , gdje R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; i X je brom ili jod, naznačen time što se sastoji u a) aktiviranju 5-brom-2-furankarboksilne kiseline ili 5-jod-2-furankarboksilne kiseline kako bi se dobilo aktivirani oblik 5-brom-2-furankarboksilne kiseline ili 5-jod-2-furankarboksilne kiseline; i b) reakciji aktiviranog oblika 5-brom-2-furankarboksilne kiseline ili 5-jod-2-furankarboksilne kiseline sa spojem formule VI [image] , gdje R1' je kao što je definirano za formulu IV, a Boc je tert-butoksikarbonil, u otapalu.
9. Postupak u skladu s patentnim zahtjevom 8, naznačen time što R1' je vodik.
10. Postupak, u skladu s patentnim zahtjevom 8 ili 9, dobivanja spoja formule IVc [image] , gdje Boc je tert-butoksikarbonil, naznačen time što se sastoji u a) obradi 5-brom-2-furankarboksilne kiseline tionil-kloridom kako bi se dobilo 5-brom-2-furoil-klorid; i b) reakciji 5-brom-2-furoil-klorida sa spojem formule VIa [image] , gdje Boc je tert-butoksikarbonil, u otapalu, u prisutnosti baze.
11. Postupak dobivanja spoja formule VI [image] , gdje R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; i Boc je tert-butoksikarbonil, ili njegove soli, naznačen time što se sastoji u a) obradi soli 3-halogenbenzilamina formule VII [image] , 1,2-bis(klordimetilsilil)etanom, u otapalu, u prisutnosti baze, kako bi se dobilo 1-(3-halogenbenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentan formule VIII [image] ; b) obradi 1-(3-halogenbenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentana formule VIII, u otapalu, alkillitijskim spojem i 1-benzil-4-piperidonom, na temperaturi od otprilike –80 °C do otprilike –40 °C, kako bi se dobilo alkohol formule IX [image] ; c) obradi alkohola formule IX kiselinom, u otapalu, kako bi se dobilo hidroksipiperidinilbenzilamin formule X [image] u obliku soli s kiselinom; d) obradi hidroksipiperidinilbenzilamina formule X, ili njegove soli, koncentriranom, neoksidirajućom kiselinom, na temperaturi od otprilike 70 °C do otprilike 150 °C, te zaluživanjem, kako bi se dobilo olefin formule XI [image] ; i e) obradi olefina formule XI di-tert-butil-dikarbonatom, u otapalu, u prisutnosti baze, kako bi se dobilo zaštićeni amin formule XII [image] , gdje Boc je tert-butoksikarbonil, te gdje Ph u formulama IX, X, XI i XII je fenil, X' u formulama VII i VIII je brom ili jod, a R1' u formulama VII, VIII, IX, X, XI i XII je kao što je definirano za formulu VI.
12. Postupak, u skladu s patentnim zahtjevom 11, dobivanja 4-[3-(tert-butoksikarbonilaminometil)fenil] piperidina, ili njegove soli, naznačen time što se sastoji u a) obradi 3-brombenzilamin-hidroklorida ili 3-jodbenzilamin-hidroklorida 1,2-bis(klordimetilsilil) etanom, u halogeniranom alifatskom ugljikovodiku, u prisutnosti tercijarnog amina, kako bi se dobilo odgovarajući 1-(3-halogenbenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentan, gdje halo je brom ili jod; b) obradi 1-(3-halogenbenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentana, u eteru, alkillitijskim spojem i 1-benzil-4-piperidonom, na temperaturi od otprilike –80 °C do otprilike –40 °C, kako bi se dobilo 1-[3-(1-benzil-4-hidroksipiperidin-4-il)benzil]-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentan; c) obradi 1-[3-(1-benzil-4-hidroksipiperidin-4-il)benzil]-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentana anorganskom kiselinom, u halogeniranom ugljikovodiku, kako bi se dobilo 3-(1-benzil-4-hidroksipiperidin-4-il)benzilamin u obliku soli s anorganskom kiselinom; d) obradi 3-(1-benzil-4-hidroksipiperidin-4-il)benzilamin koncentriranom, neoksidirajućom kiselinom, na temperaturi od otprilike 70 °C do otprilike 150 °C, te zaluživanjem, kako bi se dobilo 3-(1-benzil-1,2,3,6-tetrahidropiridin-4-il)benzilamin; i e) obradi 3-(1-benzil-1,2,3,6-tetrahidropiridin-4-il)benzilamina di-tert-butil-dikarbonatom, u alifatskom alkoholu, etil-acetatu, eteru, halogeniranom ugljikovodiku, smjesi dva ili više takvih otapala ili smjesi jednog ili više takvih otapala s vodom, u prisutnosti hidroksida, karbonata ili alkoholata alkalnog metala ili tercijarnog amina, kako bi se dobilo tert-butilni ester 3-(1-benzil-1,2,3,6-tetrahidropiridin-4-il)benzilkarbaminske kiseline.
13. Postupak u skladu s patentnim zahtjevima 11 ili 12, naznačen time što se dodatno sastoji u obradi amina formule XII vodikom, u otapalu, u prisutnosti paladijskog katalizatora i u prisutnosti kiseline, kako bi se dobilo spoj formule VI, ili njegovu sol.
14. Postupak dobivanja spoja formule VI [image] , gdje R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; i Boc je tert-butoksikarbonil, ili njegove soli, naznačen time što se sastoji u a) obradi 3-(4-piridil)benzaldehida formule XIII [image] , hidroksilaminom ili solju hidroksilamina u otapalu, kako bi se dobilo oksim formule XIV, ili njegovu sol [image] ; b) obradi oksima formule XIV, ili njegove soli, vodikom, u otapalu, u prisutnosti paladijskog katalizatora, kako bi se dobilo 3-(4-piridil)benzilamin formule XV, ili njegovu sol [image] ; c) obradi 3-(4-piridil)benzilamina formule XV, ili njegove soli, di-tert-butil-dikarbonatom, u otapalu, u prisutnosti baze, kako bi se dobilo Boc-zaštićeni 3-(4-piridil)benzilamin formule XVI [image] , gdje Boc je tert-butoksikarbonil; i d) obradi Boc-zaštićenog 3-(4-piridil)benzilamina formule XVI vodikom, u otapalu, u prisutnosti platinskog katalizatora i u prisutnosti kiseline, kako bi se dobilo spoj formule VI, ili njegovu sol; gdje R1' u formulama XIII, XIV, XV i XVI je kao što je definirano gore, za formulu VI.
15. Postupak, u skladu s patentnim zahtjevom 14, dobivanja 4-[3-(tert-butoksikarbonilaminometil)fenil] piperidina, ili njegove soli, naznačen time što se sastoji u a) obradi 3-(4-piridil)benzaldehida hidroksilaminom, ili njegovom solju, u alifatskom alkoholu, na temperaturi od otprilike 0 °C do otprilike 40 °C, kako bi se dobilo 3-(4-piridil)benzaldehid-oksim, ili njegovu sol; b) obradi 3-(4-piridil)benzaldehid-oksima, ili njegove soli, vodikom, pod tlakom od otprilike 300 kPa do otprilike 1500 kPa, u alifatskom alkoholu, u prisutnosti paladijskog katalizatora, na temperaturi od otprilike 20 °C do otprilike 50 °C, kako bi se dobilo 3-(4-piridil)benzilamin, ili njegovu sol; c) obradi 3-(4-piridil)benzilamina, ili njegove soli, di-tert-butil-dikarbonatom, u alifatskom alkoholu, etil-acetatu, eteru, halogeniranom ugljikovodiku, smjesi dva ili više takvih otapala ili smjesi jednog ili više takvih otapala s vodom, u prisutnosti hidroksida, karbonata ili alkoholata alkalnog metala ili tercijarnog amina, kako bi se dobilo tert-butilni ester 3-(4-piridil)benzilkarbaminske kiseline; i d) obradi tert-butilnog estera 3-(4-piridil)benzilkarbaminske kiseline vodikom, u alifatskom alkoholu, pod tlakom od otprilike 2000 kPa do otprilike 6000 kPa, u prisutnosti platinskog katalizatora i u prisutnosti kiseline.
16. Postupak dobivanja spoja formule VI [image] , gdje R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; i Boc je tert-butoksikarbonil, ili njegove soli, naznačen time što se sastoji u a) obradi 3-(4-piridil)benzonitrila formule XVII, [image] , vodikom, u prisutnosti paladijskog katalizatora i u prisutnosti kiseline, ili kompleksnim hidridom, u otapalu, kako bi se dobilo 3-(4-piridil)benzilamin formule XV, ili njegovu sol [image] ; b) obradi 3-(4-piridil)benzilamina formule XV, ili njegove soli, di-tert-butil-dikarbonatom, u otapalu, u prisutnosti baze, kako bi se dobilo Boc-zaštićeni 3-(4-piridil)benzilamin formule XVI [image] , gdje Boc je tert-butoksikarbonil; i c) obradi Boc-zaštićenog 3-(4-piridil)benzilamina formule XVI vodikom, u otapalu, u prisutnosti platinskog katalizatora i u prisutnosti kiseline, kako bi se dobilo spoj formule VI, ili njegovu sol; gdje R1' u formuli XV, XVI i XVII je kao što je definirano gore, za formulu VI.
17. Postupak, u skladu s patentnim zahtjevom 16, dobivanja 4-[3-(tert-butoksikarbonilaminometil)fenil] piperidina, ili njegove soli, naznačen time što se sastoji u a) obradi 3-(4-piridil)benzonitrila vodikom, u prisutnosti paladijskog katalizatora, pod tlakom od otprilike 2000 kPa do otprilike 6000 kPa, u alifatskom alkoholu ili smjesi alifatskog alkohola s vodom, ili kompleksnim hidridom, u alifatskom alkoholu ili eteru, na temperaturi od otprilike 0 °C do otprilike 50 °C, kako bi se dobilo 3-(4-piridil)benzilamin, ili njegovu sol; b) obradi 3-(4-piridil)benzilamina, ili njegove soli, di-tert-butil-dikarbonatom, u alifatskom alkoholu, etil-acetatu, eteru, halogeniranom ugljikovodiku, smjesi dva ili više takvih otapala ili smjesi jednog ili više takvih otapala s vodom, u prisutnosti hidroksida, karbonata ili alkoholata alkalnog metala ili tercijarnog amina, kako bi se dobilo tert-butilni ester 3-(4-piridil)benzilkarbaminske kiseline; i c) obradi tert-butilnog estera 3-(4-piridil)benzilkarbaminske kiseline vodikom u alifatskom alkoholu, pod tlakom od otprilike 2000 kPa do otprilike 6000 kPa, u prisutnosti platinskog katalizatora i u prisutnosti kiseline.
18. Spoj formule VIII [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; a X' je brom ili jod; s izuzetkom 1-(3-brombenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentana.
19. Spoj u skladu s patentnim zahtjevom 18, naznačen time što navedeni spoj je 1-(3-jodbenzil)-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentan.
20. Spoj formule IX [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; a Ph je fenil.
21. Spoj u skladu s patentnim zahtjevom 20, naznačen time što navedeni spoj je 1-[3-(1-benzil-4-hidroksipiperidin-4-il)benzil]-2,2,5,5-tetrametil-1-aza-2,5-disilaciklopentan.
22. Spoj formule X [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; a Ph je fenil, ili njegova sol.
23. Spoj u skladu s patentnim zahtjevom 22, naznačen time što navedeni spoj je 3-(1-benzil-4-hidroksipiperidin-4-il)benzilamin, ili njegova sol.
24. Spoj formule XI [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; a Ph je fenil, ili njegova sol.
25. Spoj u skladu s patentnim zahtjevom 24, naznačen time što navedeni spoj je 3-(1-benzil-1,2,3,6-tetrahidropiridin-4-il)benzilamin, ili njegova sol.
26. Spoj formule XII [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; Boc je tert-butoksikarbonil; a Ph je fenil, ili njegova sol.
27. Spoj u skladu s patentnim zahtjevom 26, naznačen time što navedeni spoj je tert-butilni ester 3-(1-benzil-1,2,3,6-tetrahidropiridin-4-il)benzilkarbaminske kiseline, ili njegova sol.
28. Spoj formule XIV [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak, ili njegova sol.
29. Spoj u skladu s patentnim zahtjevom 28, naznačen time što navedeni spoj je 3-(4-piridil)benzaldehid-oksim, ili njegova sol.
30. Spoj formule XV [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak, ili njegova sol.
31. Spoj u skladu s patentnim zahtjevom 30, naznačen time što navedeni spoj je 3-(4-piridil)benzilamin, ili njegova sol.
32. Spoj formule XVI [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; a Boc je tert-butoksikarbonil, ili njegova sol.
33. Spoj u skladu s patentnim zahtjevom 32, naznačen time što navedeni spoj je tert-butilni ester 3-(4-piridil) benzilkarbaminske kiseline, ili njegova sol.
34. Spoj formule IVb [image] , naznačen time što R1' je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino, ili njegov zaštićeni derivat ili njegov predostatak; i Boc je tert-butoksikarbonil, ili njegova sol.
35. Spoj u skladu s patentnim zahtjevom 34, naznačen time što navedeni spoj je 4-[3-(tert-butoksikarbonilaminometil)fenil]-1-[5-brom-2-furanoil]piperidin.
36. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 18 do 35, naznačena time što je navedeni spoj međuprodukt u dobivanju spoja formule I [image] , gdje R1 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, di((C1-C8)-alkil)amino, di((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; i R2 je H, F, CF3, OCF3, (C1-C8)-alkil, (C3-C10)-cikloalkil, 3- do 10- člani heterocikloalkil, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C6-C14)-aril, 5- do 10- člani heteroaril, koji sadrži 1, 2 ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, (C1-C8)-alkoksi, (C3-C10)-cikloalkoksi, (C6-C14)-ariloksi, 5- do 10- člani heteroariloksi, koji sadrži 1, 2, ili 3 istovjetna ili različita heteroatoma u prstenu, koje se bira između dušika, kisika i sumpora, di((C1-C8)-alkil)amino, di-((C3-C10)-cikloalkil)amino ili di((C6-C14)-aril)amino; ili njegove soli.
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IL177423A0 (en) 2006-12-10
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