HRP20171167T1 - Priprava intermedijera pirimidina koji služe za proizvodnju macitentana - Google Patents
Priprava intermedijera pirimidina koji služe za proizvodnju macitentana Download PDFInfo
- Publication number
- HRP20171167T1 HRP20171167T1 HRP20171167TT HRP20171167T HRP20171167T1 HR P20171167 T1 HRP20171167 T1 HR P20171167T1 HR P20171167T T HRP20171167T T HR P20171167TT HR P20171167 T HRP20171167 T HR P20171167T HR P20171167 T1 HRP20171167 T1 HR P20171167T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- formula
- reaction
- toluene
- mixture
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 0.000 title 1
- 229960001039 macitentan Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 18
- 238000000034 method Methods 0.000 claims 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 12
- 150000003839 salts Chemical class 0.000 claims 9
- 238000006243 chemical reaction Methods 0.000 claims 8
- 239000000010 aprotic solvent Substances 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 229910003074 TiCl4 Inorganic materials 0.000 claims 5
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 239000003513 alkali Substances 0.000 claims 3
- BDLXTDLGTWNUFM-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]ethanol Chemical compound CC(C)(C)OCCO BDLXTDLGTWNUFM-UHFFFAOYSA-N 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
Claims (15)
1. Spoj, naznačen time, da ima sljedeću formulu I-2:
[image]
I-2
ili njegova sol.
2. Postupak za proizvodnju spoja formule I2 prema zahtjevu 1, naznačen time, da spomenuti postupak obuhvaća reakciju spoja sljedeće formule I1:
[image]
I-1
gdje G1 predstavlja halogen, ili soli navedenog spoja,
s 2(tertbutoksi)etanolom u prisutnosti lužine na temperaturi od 25 do 140°C.
3. Postupak prema zahtjevu 2, naznačen time, da je spoj formule I-1 takav, da G1 predstavlja klor.
4. Postupak prema zahtjevu 2 ili 3, naznačen time, da je lužina odabrana iz skupine koju čine NaOH, KOH i kalijev tert-butilat.
5. Postupak prema jednom od zahtjeva 2 do 4, naznačen time, da se izvodi u aprotonskom otapalu ili u smjesi otapala koja se sastoji od diklorometana, toluena, ili od mješavine diklorometana i toluena.
6. Uporaba spoja formule I2 kako je definirano u zahtjevu 1, naznačena time, da služi u postupku proizvodnje spoja sljedeće formule I3:
[image]
I-3
ili njegove soli.
7. Postupak za proizvodnju spoja sljedeće formule I3:
[image]
I-3
ili njegove soli, naznačen time, da spomenuti postupak obuhvaća reakciju spoja formule I2 kako je definirano u zahtjevu 1, ili soli navedenog spoja,
s TiCl4 u aprotonskom otapalu ili u smjesi aprotonskih otapala.
8. Postupak prema zahtjevu 7, naznačen time, da aprotonsko otapalo ili smjesa aprotonskih otapala treba sadržavati toluen, diklorometan ili mješavinu toluena i diklorometana.
9. Postupak prema zahtjevu 7, naznačen time, da se reakcija spoja formule I2 s TiCl4, provodi u toluenu.
10. Postupak prema jednom od zahtjeva 7 do 9, naznačen time, da se reakcija spoja formule I2 s TiCl4, izvodi na temperaturi od 10 do 100°C.
11. Postupak prema zahtjevu 10, naznačen time, da se reakcija spoja formule I2 s TiCl4, izvodi na temperaturi od 20 do 70°C.
12. Postupak za proizvodnju spoja sljedeće formule I3:
[image]
I-3
ili njegove soli, naznačen time, da navedeni postupak obuhvaća sljedeće korake:
reakcija spoja sljedeće formule I1:
[image]
I-1
gdje G1 predstavlja halogen, ili soli navedenog spoja,
s 2(tertbutoksi)etanolom u prisutnosti lužine na temperaturi od 25 do 140°C, kako bi se dobio spoj formule I2 kao što je definirano u zahtjevu 1, ili sol navedenog spoja, i
reakcija spoja ili soli dobivenog/dobivene u koraku a) s TiCl4 u aprotonskom otapalu ili u smjesi otapala.
13. Postupak prema zahtjevu 12, naznačen time, da je spoj formule I-1 takav, da G1 predstavlja klor.
14. Postupak prema zahtjevu 12 ili 13, naznačen time, da se obje reakcije iz koraka a) i b) iz postupka u skladu sa zahtjevom 12 ili 13, provode u toluenu.
15. Postupak prema jednom od zahtjeva 12 do 14, naznačen time, da se ne izolira produkt koji se dobiva nakon koraka a), a koraci a) i b) se izvode u istom reaktoru.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13161422 | 2013-03-27 | ||
| EP14717209.2A EP2978746B1 (en) | 2013-03-27 | 2014-03-26 | Preparation of pyrimidine intermediates useful for the manufacture of macitentan |
| PCT/IB2014/060160 WO2014155304A1 (en) | 2013-03-27 | 2014-03-26 | Preparation of pyrimidine intermediates useful for the manufacture of macitentan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20171167T1 true HRP20171167T1 (hr) | 2017-10-06 |
Family
ID=47997198
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20171167TT HRP20171167T1 (hr) | 2013-03-27 | 2017-07-31 | Priprava intermedijera pirimidina koji služe za proizvodnju macitentana |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US9422249B2 (hr) |
| EP (1) | EP2978746B1 (hr) |
| JP (1) | JP6421172B2 (hr) |
| KR (1) | KR102283931B1 (hr) |
| CN (1) | CN105073716B (hr) |
| AR (1) | AR095727A1 (hr) |
| CA (1) | CA2900911C (hr) |
| DK (1) | DK2978746T3 (hr) |
| ES (1) | ES2636864T3 (hr) |
| HR (1) | HRP20171167T1 (hr) |
| HU (1) | HUE035760T2 (hr) |
| IL (1) | IL241758B (hr) |
| MX (1) | MX359673B (hr) |
| PL (1) | PL2978746T3 (hr) |
| PT (1) | PT2978746T (hr) |
| TW (1) | TWI634108B (hr) |
| WO (1) | WO2014155304A1 (hr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR095727A1 (es) | 2013-03-27 | 2015-11-04 | Actelion Pharmaceuticals Ltd | Preparación de intermediarios de pirimidina |
| EP2907811A1 (en) | 2014-02-14 | 2015-08-19 | Actelion Pharmaceuticals Ltd. | Process for manufacturing pyrimidine sulfamide derivatives |
| CN105461637A (zh) * | 2014-09-11 | 2016-04-06 | 天津市医药集团技术发展有限公司 | 一种马西替坦晶型及其制备方法 |
| CN105622523A (zh) * | 2014-10-28 | 2016-06-01 | 四川海思科制药有限公司 | 一种n-[5-(4-溴苯基)-6-[2-[(5-溴-2-嘧啶基)氧]乙氧基]-4-嘧啶基]-n’-丙基磺酰胺化合物 |
| CN104897833B (zh) * | 2015-05-15 | 2017-03-01 | 成都克莱蒙医药科技有限公司 | 一种马西替坦中间体的检测方法及其应用 |
| CN106279043B (zh) * | 2015-06-05 | 2020-12-22 | 江苏豪森药业集团有限公司 | 马西替坦相关物质的制备方法 |
| ZA201605808B (en) | 2015-08-26 | 2017-08-30 | Cipla Ltd | Process for preparing an endothelin receptor antagonist |
| CN105461639B (zh) * | 2015-12-10 | 2018-03-09 | 合肥久诺医药科技有限公司 | 一种高纯度马西替坦的精制方法 |
| CN105461638A (zh) * | 2015-12-10 | 2016-04-06 | 合肥久诺医药科技有限公司 | 一种马西替坦晶型及其制备方法 |
| WO2017191565A1 (en) * | 2016-05-04 | 2017-11-09 | Shilpa Medicare Limited | Process for preparation of macitentan |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6136971A (en) | 1998-07-17 | 2000-10-24 | Roche Colorado Corporation | Preparation of sulfonamides |
| PT1254121E (pt) * | 2000-01-25 | 2006-06-30 | Hoffmann La Roche | Preparacao de sulfonamidas |
| IL155805A0 (en) * | 2000-12-18 | 2003-12-23 | Actelion Pharmaceuticals Ltd | Novel sulfamides and their use as endothelin receptor antagonists |
| TW200628467A (en) * | 2004-11-11 | 2006-08-16 | Actelion Pharmaceuticals Ltd | Novel sulfamides |
| AR095727A1 (es) | 2013-03-27 | 2015-11-04 | Actelion Pharmaceuticals Ltd | Preparación de intermediarios de pirimidina |
| EP2907811A1 (en) | 2014-02-14 | 2015-08-19 | Actelion Pharmaceuticals Ltd. | Process for manufacturing pyrimidine sulfamide derivatives |
-
2014
- 2014-03-25 AR ARP140101342A patent/AR095727A1/es unknown
- 2014-03-26 KR KR1020157030777A patent/KR102283931B1/ko active IP Right Grant
- 2014-03-26 MX MX2015013745A patent/MX359673B/es active IP Right Grant
- 2014-03-26 PT PT147172092T patent/PT2978746T/pt unknown
- 2014-03-26 PL PL14717209T patent/PL2978746T3/pl unknown
- 2014-03-26 DK DK14717209.2T patent/DK2978746T3/en active
- 2014-03-26 HU HUE14717209A patent/HUE035760T2/en unknown
- 2014-03-26 EP EP14717209.2A patent/EP2978746B1/en active Active
- 2014-03-26 JP JP2016504838A patent/JP6421172B2/ja active Active
- 2014-03-26 CA CA2900911A patent/CA2900911C/en active Active
- 2014-03-26 WO PCT/IB2014/060160 patent/WO2014155304A1/en active Application Filing
- 2014-03-26 US US14/780,383 patent/US9422249B2/en active Active
- 2014-03-26 ES ES14717209.2T patent/ES2636864T3/es active Active
- 2014-03-26 CN CN201480018828.8A patent/CN105073716B/zh active Active
- 2014-03-26 TW TW103111324A patent/TWI634108B/zh active
-
2015
- 2015-09-21 IL IL241758A patent/IL241758B/en active IP Right Grant
-
2016
- 2016-07-14 US US15/210,255 patent/US9676731B2/en active Active
-
2017
- 2017-07-31 HR HRP20171167TT patent/HRP20171167T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL2978746T3 (pl) | 2017-10-31 |
| CN105073716A (zh) | 2015-11-18 |
| AR095727A1 (es) | 2015-11-04 |
| US9422249B2 (en) | 2016-08-23 |
| EP2978746B1 (en) | 2017-05-10 |
| US9676731B2 (en) | 2017-06-13 |
| DK2978746T3 (en) | 2017-07-10 |
| JP2016515570A (ja) | 2016-05-30 |
| US20160318879A1 (en) | 2016-11-03 |
| PT2978746T (pt) | 2017-08-11 |
| ES2636864T3 (es) | 2017-10-09 |
| TW201514155A (zh) | 2015-04-16 |
| CA2900911A1 (en) | 2014-10-02 |
| KR20150134415A (ko) | 2015-12-01 |
| HUE035760T2 (en) | 2018-05-28 |
| TWI634108B (zh) | 2018-09-01 |
| CN105073716B (zh) | 2018-02-09 |
| JP6421172B2 (ja) | 2018-11-07 |
| MX359673B (es) | 2018-10-05 |
| EP2978746A1 (en) | 2016-02-03 |
| CA2900911C (en) | 2020-10-13 |
| MX2015013745A (es) | 2016-02-26 |
| KR102283931B1 (ko) | 2021-07-30 |
| IL241758B (en) | 2019-05-30 |
| US20160052891A1 (en) | 2016-02-25 |
| WO2014155304A1 (en) | 2014-10-02 |
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