HRP20171901T1 - Postupak za dobivanje modulatora cistično fibroznog regulatora transmembranske vodljivosti - Google Patents

Postupak za dobivanje modulatora cistično fibroznog regulatora transmembranske vodljivosti Download PDF

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Publication number
HRP20171901T1
HRP20171901T1 HRP20171901TT HRP20171901T HRP20171901T1 HR P20171901 T1 HRP20171901 T1 HR P20171901T1 HR P20171901T T HRP20171901T T HR P20171901TT HR P20171901 T HRP20171901 T HR P20171901T HR P20171901 T1 HRP20171901 T1 HR P20171901T1
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Croatia
Prior art keywords
compound
image
formula
dichloromethane
formyl
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HRP20171901TT
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English (en)
Inventor
John Demattei
Adam R. Looker
Bobbiana Neubert-Langille
Martin Trudeau
Stefanie Roper
Michael Ryan
Dahrika Milfred Lao Yap
Brian R. Krueger
Peter D. J. Grootenhuis
Frederick F. Van Groor
Martyn C. Botfield
Gregor Zlokarnik
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Vertex Pharmaceuticals Incorporated
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Publication of HRP20171901T1 publication Critical patent/HRP20171901T1/hr

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    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Claims (16)

1. Postupak za dobivanje spoja koji ima formulu 8 [image] koji obuhvaća nitriranje spoja koji ima formulu 7 upotrebom smjese sumporne kiseline i dušične kiseline u prisutnosti diklorometana [image] naznačen time da PG je zaštitna skupina i R2 i R4 su svaki terc-butil, te pri čemu se nitro spoj koji ima formulu 8 pročišćava kristalizacijom, pri čemu je PG propoksi formil, metansulfonil, 4-nitro-benzoil, etoksi formil, butoksi formil, t-butoksi formil, i-propoksi formil ili metoksi formil.
2. Postupak prema zahtjevu 1, naznačen time da je PG metoksi formil.
3. Postupak prema zahtjevu 1, naznačen time da nadalje obuhvaća proizvodnju spoja s formulom 7 reakcijom spoja s formulom 6 [image] s reagensom koji može uzrokovati da se zaštitna skupina veže za fenolni kisik spoja koji s formulom 6 u prisutnosti otapala.
4. Postupak prema zahtjevu 3, naznačen time da je otapalo dietil eter, ili metilen klorid.
5. Postupak prema zahtjevu 4, naznačen time da je otapalo metilen klorid.
6. Postupak prema zahtjevu 1, naznačen time da nadalje sadrži dobivanje spoja s formulom 5 [image] redukcijom spoja s formulom 8.
7. Postupak za dobivanje spoja 31, naznačen time da sadrži dovođenje u kontakt spoja 30 sa smjesom dušične kiseline i sumporne kiseline u prisutnosti diklorometana. [image]
8. Postupak prema zahtjevu 7, naznačen time da se reakcija gasi dodavanjem reakcijske smjese u hladnu vodu.
9. Postupak prema zahtjevu 8, naznačen time da se vodeni sloj ekstrahira upotrebom diklorometana.
10. Postupak prema zahtjevu 9, naznačen time da se diklorometan nadalje ispire s vodom.
11. Postupak prema zahtjevu 7, naznačen time da se proizvod izolira kristalizacijom s heksanom.
12. Postupak prema zahtjevu 7, naznačen time da nadalje sadrži dovođenje u kontakt spoja 31 u prisutnosti plinovitog vodika, paladija na ugljiku, te metanola da se dobije spoj 32. [image]
13. Postupak prema bilo kom prethodnom zahtjevu, naznačen time da postupak nadalje sadrži dobivanje spoja koji ima strukturu: [image]
14. Spoj naznačen time da se bira od spoja 32 i spoja 33: [image] i [image]
15. Spoj prema zahtjevu 14, naznačen time da spoj je spoj 32.
16. Spoj prema zahtjevu 14, naznačen time da spoj je spoj 33.
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