HRP20211915T1 - Poboljšani postupak dobivanja r-6-hidroksi-8-[1-hidroksi-2-[2-(4-metoksifenil)-1,1-dimetiletilaminoetil]-2h-1,4-benzoksazin-3(4h)-on-hidroklorida - Google Patents
Poboljšani postupak dobivanja r-6-hidroksi-8-[1-hidroksi-2-[2-(4-metoksifenil)-1,1-dimetiletilaminoetil]-2h-1,4-benzoksazin-3(4h)-on-hidroklorida Download PDFInfo
- Publication number
- HRP20211915T1 HRP20211915T1 HRP20211915TT HRP20211915T HRP20211915T1 HR P20211915 T1 HRP20211915 T1 HR P20211915T1 HR P20211915T T HRP20211915T T HR P20211915TT HR P20211915 T HRP20211915 T HR P20211915T HR P20211915 T1 HRP20211915 T1 HR P20211915T1
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- Croatia
- Prior art keywords
- camphorsulfonate salt
- compound
- camphorsulfonate
- formula
- salt
- Prior art date
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims 9
- 238000000034 method Methods 0.000 title claims 8
- 238000004519 manufacturing process Methods 0.000 title 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims 14
- 150000001875 compounds Chemical class 0.000 claims 8
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims 5
- COUYJEVMBVSIHV-SFHVURJKSA-N olodaterol Chemical compound C1=CC(OC)=CC=C1CC(C)(C)NC[C@H](O)C1=CC(O)=CC2=C1OCC(=O)N2 COUYJEVMBVSIHV-SFHVURJKSA-N 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 229960004286 olodaterol Drugs 0.000 claims 4
- 239000002904 solvent Substances 0.000 claims 3
- MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 claims 2
- 239000012458 free base Substances 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 239000011877 solvent mixture Substances 0.000 claims 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- 239000004593 Epoxy Substances 0.000 claims 1
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 238000002329 infrared spectrum Methods 0.000 claims 1
- 239000013067 intermediate product Substances 0.000 claims 1
- 229960001733 olodaterol hydrochloride Drugs 0.000 claims 1
- -1 p-methoxybenzyl Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C309/07—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing oxygen atoms bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/255—Tartaric acid
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/60—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members
- C07C2603/66—Ring systems containing bridged rings containing three rings containing at least one ring with less than six members containing five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (13)
1. Kamforsulfonatna sol međuprodukta (4), naznačena time što je PG C1-C10alkil supstituiran s C6-C10arilnom skupinom
[image]
.
2. Kamforsulfonatna sol u skladu s patentnim zahtjevom 1, naznačena time što je PG benzil ili p-metoksibenzil.
3. Kamforsulfonatna sol u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što je molarni omjer između međuprodukta (4) i kamforsulfonske kiseline 1:1.
4. Kamforsulfonatna sol u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačena time što je kamforsulfonska kiselina (R)-(–)-kamforsulfonska kiselina.
5. Kamforsulfonatna sol u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačena time što je kamforsulfonska kiselina (S)-(+)-kamforsulfonska kiselina.
6. Kamforsulfonatna sol u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačena time što je u kristalnom čvrstom obliku.
7. Kristalni čvrsti oblik kamforsulfonatne soli u skladu s patentnim zahtjevom 6, naznačen time što ima najmanje jedno od sljedećeg:
a) DSC termogram koji pokazuje endotermni maksimum s početkom na 163-166 °C, ili
b) IR spektre koji pokazje sljedeće vrpce na 2955, 1745, 1702, 1617, 1513, 1470, 1369, 1329, 1250, 1162, 1051, 1038, 852, 746, 700 cm–1.
8. Postupak priprave kamforsulfonatne soli u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što se sastoji u koracima:
a) obrade međuprodukta formule (4)
[image]
,
gdje je PG u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, kamforsulfonskom kiselinom u prisutnosti otapala ili smjese otapala, i
b) izdvajanja kamforsulfonatne soli dobivene u koraku a).
9. Postupak dobivanja olodaterola, ili njegove farmaceutski prihvatljive soli, naznačen time što se sastoji u koracima:
a) osiguravanja kamforsulfonatne soli spoja (4) u skladu s bilo kojim od patentnih zahtjeva 1 do 7,
b) izborne obrade kamforsulfonatne soli spoja (4) klorovodičnom kiselinom kako bi se dobilo spoj formule (4)·HX
[image]
,
gdje je PG zaštitna skupina za hidroksil kao što je definirana u koraku a), a HX je klorovodična kiselina,
c) uklanjanja zaštitne skupine za hidroksil PG iz produkata iz koraka a) ili b) hidrogeniranjem u prisutnosti katalizatora i organskog otapala kako bi se dobilo olodaterol, ili njegovu farmaceutski prihvatljivu sol, te
d) izborne obrade olodaterola dobivenog u koraku c) farmaceutski prihvatljivom kiselinom kako bi se dobilo njegovu farmaceutski prihvatljivu sol.
10. Postupak u skladu s patentnim zahtjevom 9, naznačen time što se korak b) provodi i uključuje dodatne korake:
b1) prevođenja kamforsulfonatne soli spoja (4), u skladu s bilo kojim od patentnih zahtjeva 1 do 7, u slobodnu bazu u prisutnosti baze i otapala, te
b2) obrade slobodne baze dobivene u koraku b1) klorovodičnom kiselinom kako bi se dobilo spoj formule (4) HX, gdje je HX klorovodična kiselina.
11. Postupak u skladu s bilo kojim od patentnih zahtjeva 9 do 10, naznačen time što je kamforsulfonatna sol u koraku a) (R)-(–)-kamforsulfonatna sol.
12. Postupak u skladu s bilo kojim od patentnih zahtjeva 9 do 11, naznačen time što se kamforsulfonatnu sol spoja (4) dobiva postupkom koji se sastoji u koracima:
a) reakcije amina formule (3)
[image]
,
ili njegove soli, epoksidom formule (2)
[image]
,
gdje je PG zaštitna skupina za hidroksil u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, u prisutnosti organskog otapala kako bi se dobilo spoj formule (4)
[image]
,
b) obrade spoja formule (4) dobivenog u koraku a) kamforsulfonskom kiselinom u prisutnosti otapala ili smjese otapala, gdje je PG zaštitna skupina za hidroksil kao što je definirana u koraku a).
13. Postupak u skladu s bilo kojim od patentnih zahtjeva 9 do 12, naznačen time što je farmaceutski prihvatljiva sol olodaterola R-enantiomer olodaterol-hidroklorida.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16382628 | 2016-12-20 | ||
| EP17382449 | 2017-07-10 | ||
| PCT/EP2017/083444 WO2018114887A1 (en) | 2016-12-20 | 2017-12-19 | Improved process for the manufacture of r-6-hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethylethylaminoethyl]-2h-1,4-benzoxazin-3(4h)-one hydrochloride |
| EP17816861.3A EP3558954B1 (en) | 2016-12-20 | 2017-12-19 | Improved process for the manufacture of r-6-hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethylethylaminoethyl]-2h-1,4-benzoxazin-3(4h)-one hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20211915T1 true HRP20211915T1 (hr) | 2022-03-18 |
Family
ID=60702800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20211915TT HRP20211915T1 (hr) | 2016-12-20 | 2017-12-19 | Poboljšani postupak dobivanja r-6-hidroksi-8-[1-hidroksi-2-[2-(4-metoksifenil)-1,1-dimetiletilaminoetil]-2h-1,4-benzoksazin-3(4h)-on-hidroklorida |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10800748B2 (hr) |
| EP (1) | EP3558954B1 (hr) |
| JP (1) | JP7116060B2 (hr) |
| CN (1) | CN110114346B (hr) |
| DK (1) | DK3558954T3 (hr) |
| ES (1) | ES2900283T3 (hr) |
| HR (1) | HRP20211915T1 (hr) |
| PL (1) | PL3558954T3 (hr) |
| WO (1) | WO2018114887A1 (hr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109096218B (zh) * | 2018-08-06 | 2020-10-27 | 上海方予健康医药科技有限公司 | 盐酸奥达特罗晶型a及其制备方法 |
| CN108997248B (zh) * | 2018-08-06 | 2023-08-01 | 上海方予健康医药科技有限公司 | 盐酸奥达特罗晶型b及其制备方法 |
| CN108822054B (zh) * | 2018-08-06 | 2021-06-22 | 上海方予健康医药科技有限公司 | 盐酸奥达特罗晶型c及其制备方法 |
| CN114057590A (zh) * | 2021-11-12 | 2022-02-18 | 安徽有吉医药科技有限公司 | 一种奥达特罗关键中间体的合成方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10253282A1 (de) | 2002-11-15 | 2004-05-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittel zur Behandlung von chronisch obstruktiver Lungenerkrankung |
| DE102004024454A1 (de) | 2004-05-14 | 2005-12-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Enantiomerenreine Betaagonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| ES2530991T3 (es) * | 2005-08-15 | 2015-03-09 | Boehringer Ingelheim Int | Procedimiento para la obtención de betamiméticos |
| ATE518847T1 (de) | 2007-01-25 | 2011-08-15 | Boehringer Ingelheim Int | Verfahren zur herstellung von betamimetika |
| US20100249550A1 (en) | 2009-03-25 | 2010-09-30 | Neilcor Puritan Bennett LLC | Method And Apparatus For Optical Filtering Of A Broadband Emitter In A Medical Sensor |
-
2017
- 2017-12-19 HR HRP20211915TT patent/HRP20211915T1/hr unknown
- 2017-12-19 US US16/465,762 patent/US10800748B2/en active Active
- 2017-12-19 ES ES17816861T patent/ES2900283T3/es active Active
- 2017-12-19 DK DK17816861.3T patent/DK3558954T3/da active
- 2017-12-19 PL PL17816861T patent/PL3558954T3/pl unknown
- 2017-12-19 EP EP17816861.3A patent/EP3558954B1/en active Active
- 2017-12-19 WO PCT/EP2017/083444 patent/WO2018114887A1/en unknown
- 2017-12-19 JP JP2019529170A patent/JP7116060B2/ja active Active
- 2017-12-19 CN CN201780078487.7A patent/CN110114346B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3558954B1 (en) | 2021-11-03 |
| JP7116060B2 (ja) | 2022-08-09 |
| PL3558954T3 (pl) | 2022-01-31 |
| WO2018114887A1 (en) | 2018-06-28 |
| CN110114346A (zh) | 2019-08-09 |
| EP3558954A1 (en) | 2019-10-30 |
| DK3558954T3 (da) | 2021-12-06 |
| JP2020502077A (ja) | 2020-01-23 |
| US20200062723A1 (en) | 2020-02-27 |
| CN110114346B (zh) | 2023-10-31 |
| ES2900283T3 (es) | 2022-03-16 |
| US10800748B2 (en) | 2020-10-13 |
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