HRP20100290T1 - Postupak priprave rosuvastatina i intermedijera - Google Patents
Postupak priprave rosuvastatina i intermedijera Download PDFInfo
- Publication number
- HRP20100290T1 HRP20100290T1 HR20100290T HRP20100290T HRP20100290T1 HR P20100290 T1 HRP20100290 T1 HR P20100290T1 HR 20100290 T HR20100290 T HR 20100290T HR P20100290 T HRP20100290 T HR P20100290T HR P20100290 T1 HRP20100290 T1 HR P20100290T1
- Authority
- HR
- Croatia
- Prior art keywords
- salt
- compound
- reacting
- formula iii
- image
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 7
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 title claims abstract 3
- 229960000672 rosuvastatin Drugs 0.000 title claims abstract 3
- 239000000543 intermediate Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract 13
- 150000001875 compounds Chemical class 0.000 claims abstract 12
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical group CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 claims abstract 7
- 150000007529 inorganic bases Chemical class 0.000 claims abstract 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract 6
- 239000001110 calcium chloride Substances 0.000 claims abstract 6
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract 6
- 150000007530 organic bases Chemical class 0.000 claims abstract 6
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims 3
- 230000007935 neutral effect Effects 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 3
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 claims 2
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 230000008030 elimination Effects 0.000 claims 2
- 238000003379 elimination reaction Methods 0.000 claims 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims 2
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000001176 L-lysyl group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 159000000003 magnesium salts Chemical class 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Postupak priprave rosuvastatina formule I, naznačen time, da sadrži jedan od sljedećih procesa: a) reagiranje spoja formule II, - gdje R predstavlja C1-4alkil osim tert-butil skupine - uz alkalijsku hidrolizu za dobivanje spoja formule III, nakon toga reagiranje s organskom ili anorganskom bazom za tvorbu soli, eliminirajući acetonidnu skupinu i reagiranje s kalcij-kloridom u bazi; ilib) reagiranje spoja formule IIIs organskom ili anorganskom bazom za tvorbu soli, eliminirajući acetonidnu skupinu i reagiranje s kalcij-kloridom u bazi; ilic) reagiranje soli spoja formule III- stvorene s organskom ili anorganskom bazom - uz eliminiranje acetonidne skupine ireagiranje s kalcij-kloridom u bazi. Patent sadrži još 7 patentnih zahtjeva.
Claims (8)
1. Postupak priprave rosuvastatina formule I,
[image]
naznačen time, da sadrži jedan od sljedećih procesa:
a) reagiranje spoja formule II,
[image]
- gdje R predstavlja C1-4alkil osim tert-butil skupine - uz alkalijsku hidrolizu za dobivanje spoja formule III,
[image]
nakon toga reagiranje s organskom ili anorganskom bazom za tvorbu soli, eliminirajući acetonidnu skupinu i reagiranje s kalcij-kloridom u bazi; ili
b) reagiranje spoja formule III
[image]
s organskom ili anorganskom bazom za tvorbu soli, eliminirajući acetonidnu skupinu i reagiranje s kalcij-kloridom u bazi; ili
c) reagiranje soli spoja formule III
[image]
- stvorene s organskom ili anorganskom bazom - uz eliminiranje acetonidne skupine i
reagiranje s kalcij-kloridom u bazi.
2. Postupak prema zahtjevu 1, naznačen time, da se tvorba soli provodi s metilaminom, dietanolaminom, etanolaminom, magnezij-sulfatom, L-lizinom, benzilaminom, L(-)-α-metil-benzilaminom ili N-metil-D-glukozaminom u neutralnom organskom otapalu, pri čemu navedeno neutralno organsko otapalo je acetonitril, etil-acetat, etanol ili tetrahidrofuran.
3. Postupak prema zahtjevima 1 do 2, naznačen time, da se eliminacija acetonidne skupine provodi u spomenutom neutralnom organskom otapalu uz prisutnost kiseline.
4. Spoj formule III, naznačen time, da je to:
[image]
i
sol stvorena od spoja formule III i od organske ili anorganske baze.
[image]
5. Sol spoja formule III prema zahtjevu 4, naznačena time, da je sol stvorena od metilamina, dietanolamina, etanolamina, magnezij-sulfata, L-lizina, benzilamina, L(-)-α-metil-benzilamina ili N-metil-D-glukozamina.
6. Sol spoja formule III prema zahtjevu 4, naznačena time, da je to sol dietanolamina od (6-{(E)-2-[4-(4-fluorfenil)-6-izopropil-2-(metansulfonil-metil-amino)-pirimidin-5-il]-vinil}-(4R, 6S)-2,2-dimetil-[1,3]dioksan-4-il)-octene kiseline.
7. Sol spoja formule III prema zahtjevu 4, naznačena time, da je to sol L-lizina od (6-{(E)-2-[4-(4-fluorfenil)-6-izopropil-2-(metansulfonil-metilamin)-pirimidin-5-il]-vinil}-(4R, 6S)-2,2-dimetil-[1,3]dioksan-4-il)-octene kiseline.
8. Sol spoja formule III prema zahtjevu 4, naznačena time, da je to magnezijeva sol od (6-{(E)-2-[4-(4-fluorfenil)-6-izopropil-2-(metansulfonil-metilamin)-pirimidin-5-il]-vinil}-(4R, 6S)-2,2-dimetil-[1,3]dioksan-4-il)-octene kiseline.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU0500537A HU227120B1 (hu) | 2005-05-26 | 2005-05-26 | Eljárás rosuvastatin kalciumsójának elõállítására új intermediereken keresztül |
| PCT/HU2006/000049 WO2006126035A2 (en) | 2005-05-26 | 2006-05-26 | Process for the preparation of rosuvastatin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20100290T1 true HRP20100290T1 (hr) | 2010-06-30 |
Family
ID=89986052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20100290T HRP20100290T1 (hr) | 2005-05-26 | 2010-05-24 | Postupak priprave rosuvastatina i intermedijera |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1902036B1 (hr) |
| AT (1) | ATE461924T1 (hr) |
| DE (1) | DE602006013136D1 (hr) |
| DK (1) | DK1902036T3 (hr) |
| EA (1) | EA013304B1 (hr) |
| ES (1) | ES2342788T3 (hr) |
| HR (1) | HRP20100290T1 (hr) |
| HU (1) | HU227120B1 (hr) |
| ME (1) | ME01781B (hr) |
| PL (1) | PL1902036T3 (hr) |
| RS (1) | RS51205B (hr) |
| SI (1) | SI1902036T1 (hr) |
| WO (1) | WO2006126035A2 (hr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7994178B2 (en) | 2006-09-18 | 2011-08-09 | Teva Pharmaceutical Industries, Ltd. | Crystalline rosuvastatin calcium and compositions thereof for treatment of hyperlipidaemia |
| WO2009157014A2 (en) * | 2008-01-30 | 2009-12-30 | Cadila Healthcare Limited | A process for preparing hmg-coa reductase inhibitors and intermediates |
| WO2010029561A1 (en) * | 2008-09-09 | 2010-03-18 | Biocon Limited | A process for preparation of rosuvastatin acetonide calcium |
| MX2011007478A (es) | 2009-01-15 | 2011-09-15 | Sag Egis Gyogyszergyar Nylvanosan Muekoedoe Reszvenytarsa | Proceso para la preparacion de sales de rosuvastatina. |
| WO2011104725A2 (en) | 2010-02-23 | 2011-09-01 | Cadila Healthcare Limited | Hmg-coa reductase inhibitors and process for the preparation thereof |
| WO2012038785A1 (en) * | 2010-09-21 | 2012-03-29 | Biocon Limited | Polymorphs of rosuvastatin acetonide calcium ((3r,5s,6e)-7-[4-(4- fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimn)in-5- yl)vinyl)-2,2-dimethyl-l,3-dioxan-4-yl) acetic acid calcium salt |
| MX2010011006A (es) | 2010-10-06 | 2012-04-18 | Senosiain S A De C V Lab | Nueva sal de un derivado de pirimidina. |
| WO2012073256A1 (en) * | 2010-11-29 | 2012-06-07 | Cadila Healthcare Limited | Salts of rosuvastatin |
| CN102358747B (zh) * | 2011-08-30 | 2012-09-19 | 浙江宏元药业有限公司 | 瑞舒伐他汀钙中间体及制备瑞舒伐他汀钙中间体和瑞舒伐他汀钙的方法 |
| CN102796036B (zh) * | 2012-09-12 | 2014-06-04 | 江苏阿尔法药业有限公司 | 一种阿托伐他汀钙的制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9903472D0 (en) * | 1999-02-17 | 1999-04-07 | Zeneca Ltd | Chemical process |
| GB0011163D0 (en) * | 2000-05-10 | 2000-06-28 | Astrazeneca Ab | Chemical compound |
| GB0324791D0 (en) * | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
-
2005
- 2005-05-26 HU HU0500537A patent/HU227120B1/hu unknown
-
2006
- 2006-05-26 RS RSP-2010/0158A patent/RS51205B/sr unknown
- 2006-05-26 EP EP06744403A patent/EP1902036B1/en active Active
- 2006-05-26 EA EA200702579A patent/EA013304B1/ru unknown
- 2006-05-26 ES ES06744403T patent/ES2342788T3/es active Active
- 2006-05-26 PL PL06744403T patent/PL1902036T3/pl unknown
- 2006-05-26 AT AT06744403T patent/ATE461924T1/de active
- 2006-05-26 DK DK06744403.4T patent/DK1902036T3/da active
- 2006-05-26 ME MEP-2010-158A patent/ME01781B/me unknown
- 2006-05-26 SI SI200630623T patent/SI1902036T1/sl unknown
- 2006-05-26 WO PCT/HU2006/000049 patent/WO2006126035A2/en active Application Filing
- 2006-05-26 DE DE602006013136T patent/DE602006013136D1/de active Active
-
2010
- 2010-05-24 HR HR20100290T patent/HRP20100290T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006126035A2 (en) | 2006-11-30 |
| HU0500537D0 (en) | 2005-08-29 |
| HU227120B1 (hu) | 2010-07-28 |
| EP1902036A2 (en) | 2008-03-26 |
| HUP0500537A2 (en) | 2007-05-02 |
| SI1902036T1 (sl) | 2010-05-31 |
| EA013304B1 (ru) | 2010-04-30 |
| PL1902036T3 (pl) | 2010-08-31 |
| RS51205B (sr) | 2010-12-31 |
| ES2342788T3 (es) | 2010-07-14 |
| WO2006126035A3 (en) | 2007-06-14 |
| DK1902036T3 (da) | 2010-06-28 |
| ATE461924T1 (de) | 2010-04-15 |
| EP1902036B1 (en) | 2010-03-24 |
| EA200702579A1 (ru) | 2008-04-28 |
| DE602006013136D1 (de) | 2010-05-06 |
| ME01781B (me) | 2010-12-31 |
| HUP0500537A3 (en) | 2008-04-28 |
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