HRP20211193T1 - Postupak za sintezu 2-hidroksi-6-((2-(1-izopropil-1h-pirazol-5-yl)-piridin-3-yl)metoksi)benzaldehida - Google Patents

Postupak za sintezu 2-hidroksi-6-((2-(1-izopropil-1h-pirazol-5-yl)-piridin-3-yl)metoksi)benzaldehida Download PDF

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Publication number
HRP20211193T1
HRP20211193T1 HRP20211193TT HRP20211193T HRP20211193T1 HR P20211193 T1 HRP20211193 T1 HR P20211193T1 HR P20211193T T HRP20211193T T HR P20211193TT HR P20211193 T HRP20211193 T HR P20211193T HR P20211193 T1 HRP20211193 T1 HR P20211193T1
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Croatia
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compound
alkyl
image
process according
acid
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HRP20211193TT
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English (en)
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Zhe Li
Nathan GUZ
Yiyang SHAO
Julieana COCUZ
Markus Frieser
George Petros Yiannikouros
Liang LIAO
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Global Blood Therapeutics, Inc.
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Publication of HRP20211193T1 publication Critical patent/HRP20211193T1/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/56—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/56—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing hydroxy groups
    • C07C47/565—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing hydroxy groups all hydroxy groups bound to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Claims (16)

1. Postupak za sintezu Spoja (I): [image] naznačen time, da postupak obuhvaća: Korak (i): obrađivanje spoja formule (2): [image] pri čemu svaki R je -CH(CH2R1)-OR2 ili tetrahidropiran-2-il opcionalno supstituiran s jednim, dva ili tri alkila; i pritom R1 je vodik ili alkil, i R2 je alkil; s kiselinom tako da se dobije spoj (1): [image] Korak (ii): reakcija spoja (1) sa spojem formule (3): [image] gdje LG je izlazna skupina pod alkilacijskim reakcijskim uvjetima tako da se dobije Spoj (I); i Korak (iii): opcionalno kristalizacija Spoja (I) iz Koraka (ii) od heptana i metil terc-butil etera na 45° +/-5 °C do 55° +/-5 °C.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da nadalje obuhvaća formilaciju spoja formule (4): [image] kako bi se dobio spoj formule (2): [image] pri čemu svaki R u spoju formule (2) i (4) je -CH(CH2R1)-OR2 ili tetrahidropiran-2-il opcionalno supstituiran s jednim, dva ili tri alkila; i R1 je vodik ili alkil, i R2 je alkil.
3. Postupak prema patentnom zahtjevu 2, naznačen time, da nadalje obuhvaća reakciju spoja (5): [image] s vinil eterom formule CHR1=CHOR2 (gdje R1 je vodik ili alkil i R2 je alkil), ili 3,4-dihidro-2H-piranom opcionalno supstituiranim s jednim, dva ili tri alkila, u prisutnosti slabe kiseline kako bi se dobio spoj formule (4): [image] pri čemu svaki R je -CH(CH2R1)-OR2 (gdje R1 je vodik ili alkil i R2 je alkil) ili tetrahidropiran-2-il opcionalno supstituiran s jednim, dva ili tri alkila.
4. Postupak prema patentnom zahtjevu 3, naznačen time, da se spoj (4) obrađuje in situ s formilacijskim agensom tako da se dobije spoj (2).
5. Postupak prema patentnom zahtjevu 1 ili 2, naznačen time, da se spoj (2) obrađuje in situ s kiselinom tako da se dobije spoj (1).
6. Postupak prema bilo kojem od patentnih zahtjeva 1 do 5, u kojem se Spoj (I) kristalizira od heptana i metil terc-butil estera na 45° +/-5 °C do 55° +/-5 °C tako da daje Spoj (I) u bitno čistom Obliku II, naznačen time, da uzorak XRPD rendgenske difrakcije na prahu (Cu Kα radijacije) ima maksimum na jednom ili više od 13,37° 2θ, 14,37° 2θ, 19,95° 2θ ili 23,92° 2θ (od kojih je svaki ± 0,2° 2θ).
7. Postupak prema patentnom zahtjevu 6, naznačen time, da se Spoj (I) kristalizira na 45° +/-5 °C do 55° +/-5 °C tako da daje Spoj (I) pri čemu je najmanje 95% po masi od Spoja (I) u Obliku II.
8. Postupak prema bilo kojem od patentnih zahtjeva 1 do 7, naznačen time, da LG jest klor.
9. Postupak prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time, da R jest -CH(CH3)-O-CH2CH3.
10. Postupak prema bilo kojem od patentnih zahtjeva 1 do 9, naznačen time, da kiselina za odstranjivanje R skupina je anorganska kiselina.
11. Postupak prema patentnom zahtjevu 10, naznačen time, da kiselina jest klorovodična kiselina.
12. Postupak prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, da LG je klor i alkilacijska reakcija se izvodi u N-metil-2-pirolidinonu u prisutnosti natrijevog bikarbonata i katalitičke količine Nal.
13. Postupak prema bilo kojem od patentnih zahtjeva 1 do 11, u kojemu LG je klor i alkilacijska reakcija se izvodi u N-metil-2-pirolidinonu u prisutnosti natrijevog bikarbonata i katalitičke količine Nal i Spoj (I) se kristalizira od reakcijske smjese putem dodavanja vode na 40 °C do 50 °C tako da daje bitno čisti Oblik I, naznačen time, da uzorak XRPD rendgenske difrakcije na prahu (Cu Kα radijacije) ima maksimum na jednom ili više od 12,82° 2θ, 15,74° 2θ, 16,03° 2θ, 16,63° 2θ, 17,60° 2θ, 25,14° 2θ, 25,82° 2θ i 26,44° 2θ (od kojih je svaki ± 0,2° 2θ).
14. Postupak prema bilo kojem od patentnih zahtjeva 1 do 11, u kojemu LG je klor i alkilacijska reakcija se izvodi u N-metil-2-pirolidinonu u prisutnosti natrijevog bikarbonata i katalitičke količine Nal i Spoj (I) se kristalizira od reakcijske smjese putem dodavanja vode na 40 °C do 46 °C tako da daje Spoj (I) koji je najmanje 95% po masi Oblik I, naznačen time, da uzorak XRPD rendgenske difrakcije na prahu (Cu Kα radijacije) ima maksimum na jednom ili više od 12,82° 2θ, 15,74° 2θ, 16,03° 2θ, 16,63° 2θ, 17,60° 2θ, 25,14° 2θ, 25,82° 2θ i 26,44° 2θ (od kojih je svaki ± 0,2° 2θ).
15. Postupak prema bilo kojem od patentnih zahtjeva 3 do 14, naznačen time, da slaba kiselina jest piridinijev tosilat.
16. Postupak prema bilo kojem od patentnih zahtjeva 2 do 15, naznačen time, da formilacijski agens je n-BuLi i DMF.
HRP20211193TT 2016-05-12 2021-07-26 Postupak za sintezu 2-hidroksi-6-((2-(1-izopropil-1h-pirazol-5-yl)-piridin-3-yl)metoksi)benzaldehida HRP20211193T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662335583P 2016-05-12 2016-05-12
PCT/US2017/032104 WO2017197083A1 (en) 2016-05-12 2017-05-11 Process for synthesizing 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde
EP17796828.6A EP3454854B1 (en) 2016-05-12 2017-05-11 Process for synthesizing 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde

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HRP20211193T1 true HRP20211193T1 (hr) 2021-10-29

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US (5) US10077249B2 (hr)
EP (2) EP3909941A1 (hr)
JP (2) JP7398193B2 (hr)
KR (3) KR102487509B1 (hr)
CN (2) CN109152770A (hr)
AR (1) AR108435A1 (hr)
AU (2) AU2017261730B2 (hr)
BR (1) BR112018072351A2 (hr)
CA (1) CA3023662A1 (hr)
DK (1) DK3454854T3 (hr)
EA (2) EA202092636A1 (hr)
ES (1) ES2881426T3 (hr)
HR (1) HRP20211193T1 (hr)
HU (1) HUE055045T2 (hr)
IL (3) IL297055B2 (hr)
MX (3) MX2020013114A (hr)
PL (1) PL3454854T3 (hr)
PT (1) PT3454854T (hr)
SG (2) SG11201809344QA (hr)
TW (3) TWI752307B (hr)
WO (1) WO2017197083A1 (hr)

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