HRP20130300T1 - Postupak za pripravu 4-[2-(2-fluorofenoksimetil)fenil]piperidin spojeva - Google Patents

Postupak za pripravu 4-[2-(2-fluorofenoksimetil)fenil]piperidin spojeva Download PDF

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HRP20130300T1
HRP20130300T1 HRP20130300AT HRP20130300T HRP20130300T1 HR P20130300 T1 HRP20130300 T1 HR P20130300T1 HR P20130300A T HRP20130300A T HR P20130300AT HR P20130300 T HRP20130300 T HR P20130300T HR P20130300 T1 HRP20130300 T1 HR P20130300T1
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formula
compound
salt
phenyl
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HRP20130300AT
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Eric L. Stangeland
Miroslav Rapta
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Theravance, Inc.
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Publication of HRP20130300T1 publication Critical patent/HRP20130300T1/hr

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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
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    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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Claims (18)

1. Postupak za pripravu spoja prema formuli I: [image] ili njegove soli, pri čemu je: a 0, 1, 2, 3, ili 4; svaki R1 je neovisno halogen ili trifluorometil, R3 je vodik, halogen, ili -C1-6alkil; R4, R5, i R6 su nezavisno vodik ili halogen; naznačen time da se proces sastoji od sljedećih koraka: (a) reakcije spoja prema formuli 1: [image] ili njegove soli, sa spojem prema formuli 2: [image] u prisutnosti baze, čime se dobiva spoj prema formuli 3: [image] ili njegova sol, gdje je L izlazna skupina a P je amino-zaštitna skupina; i (b) uklanjanje amino-zaštitne skupine, P, iz spoja formule 3 ili njegove soli, da se dobije spoj formule I ili njegova sol.
2. Postupak prema zahtjevu 1, naznačen time da su O, R3 i R5 vodik, a R4 i R6 fluor.
3. Postupak prema zahtjevu 1, naznačen time da je L je odabran između halogenih skupina, sulfonskih skupina estera, i aciloksi skupina.
4. Postupak prema zahtjevu 3, naznačen time da je L sulfonska skupina estera sa formulom -OS(O2)-R, pri čemu je R C1-4alkil ili fenil, a fenil grupa je dodatno supstituirana s -C1-4alkil, halo ili nitro.
5. Postupak prema zahtjevu 4, naznačen time da je L-OS(O2)-CH3 ili -OSO2)-4-metilfenil.
6. Postupak prema zahtjevu 1, naznačen time da je P odabran između t-butoksikarbonil, tritil, benziloksikarbonil, 9-fluorenilmetoksikarbonil, formil, trimetilsilil i t-butildimetilsilila.
7. Postupak prema zahtjevu 6, naznačen time da je P t-butoksikarbonil.
8. Postupak prema zahtjevu 1, naznačen time da je baza u koraku (a) alkalijski metal karbonat.
9. Postupak prema zahtjevu 8, naznačen time da je alkalijski metal karbonat kalijev karbonat.
10. Postupak prema zahtjevu 1, naznačen time da se spoj prema formuli 1 ili njegova sol, pripravlja postupkom koji se sastoji od sljedećih koraka: (a') reakcije spoja prema formuli 4: [image] ili njegove soli, s redukcijskim sredstvom kako bi se dobio spoj prema formuli 5: [image] ili njegova sol; i (b') pretvaranje hidroksil skupine spoja prema formuli 5 ili njegove soli, u izlaznu skupinu, L, čime se dobiva spoj formule 1 ili njegova sol.
11. Postupak prema zahtjevu 10, naznačen time da je a 0.
12. Postupak prema zahtjevu 10, naznačen time da je L je odabran između halogenih skupina, sulfonskih skupina estera, i aciloksi skupina.
13. Postupak prema zahtjevu 12, naznačen time da je L grupa sulfonska estera koji ima formulu -OS(O2)-R, pri čemu je R-C1-4alkil ili fenil, a fenil grupa je po izboru supstituirana s -C1-4alkil, halogen ili nitro.
14. Postupak prema zahtjevu 13, naznačen time da je L-OS(O2)-CH3 ili-OS(O2)-4-metilfenil.
15. Postupak prema zahtjevu 10, naznačen time da je redukcijsko sredstvo boran dimetil sulfid kompleks ili boran-tetrahidrofuran kompleks.
16. Postupak prema zahtjevu 10, naznačen time da se p-toluensulfonil klorid ili metansulfonski anhidrid koriste u koraku (b').
17. Spoj Formule 1: [image] ili njegova sol, naznačen time da je: L bromo, jodo, ili-OS(O2)-R, gdje je R-C1-4alkil ili fenil, a fenil je po izboru supstituiran s -C1-4alkil, halo ili nitro; a je 0, 1, 2, 3, ili 4, svaki R1 je neovisno halogen ili trifluorometil, a P je amino-zaštitna skupina odabrana iz t-butoksikarbonil, tritil, benziloksikarbonil, 9-fluorenilmetoksikarbonil, formil, trimetilsilil i t-butildimetilsilil.
18. Spoj prema zahtjevu 17, naznačen time da je L-OS(O2)-R, a R je metil ili 4-metil-fenil; a je 0, a P je t-butoksikarbonil.
HRP20130300AT 2008-11-14 2013-04-02 Postupak za pripravu 4-[2-(2-fluorofenoksimetil)fenil]piperidin spojeva HRP20130300T1 (hr)

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Application Number Priority Date Filing Date Title
US11454108P 2008-11-14 2008-11-14
PCT/US2009/064304 WO2010056938A1 (en) 2008-11-14 2009-11-13 Process for preparing 4-[2-(2-fluorophenoxymethyl)phenyl]piperidine compounds

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HRP20130300T1 true HRP20130300T1 (hr) 2013-04-30

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HRP20120897AT HRP20120897T1 (hr) 2008-11-14 2012-11-07 Kristalni oblik spoja 4-[2-(2-fluorofenoksimetil)fenil]piperidina
HRP20120920AT HRP20120920T1 (hr) 2008-11-14 2012-11-13 Spojevi 4-[2-(2 fluorofenoksimetil)fenil]piperidina
HRP20130300AT HRP20130300T1 (hr) 2008-11-14 2013-04-02 Postupak za pripravu 4-[2-(2-fluorofenoksimetil)fenil]piperidin spojeva

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HRP20120897AT HRP20120897T1 (hr) 2008-11-14 2012-11-07 Kristalni oblik spoja 4-[2-(2-fluorofenoksimetil)fenil]piperidina
HRP20120920AT HRP20120920T1 (hr) 2008-11-14 2012-11-13 Spojevi 4-[2-(2 fluorofenoksimetil)fenil]piperidina

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