HRP20200821T1 - Novi procesi za pripremu vemurafeniba - Google Patents
Novi procesi za pripremu vemurafeniba Download PDFInfo
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- HRP20200821T1 HRP20200821T1 HRP20200821TT HRP20200821T HRP20200821T1 HR P20200821 T1 HRP20200821 T1 HR P20200821T1 HR P20200821T T HRP20200821T T HR P20200821TT HR P20200821 T HRP20200821 T HR P20200821T HR P20200821 T1 HRP20200821 T1 HR P20200821T1
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- 238000000034 method Methods 0.000 title claims 19
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 title 1
- 229960003862 vemurafenib Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 33
- 238000006243 chemical reaction Methods 0.000 claims 12
- 238000006114 decarboxylation reaction Methods 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 125000002560 nitrile group Chemical group 0.000 claims 4
- RTAWCKGXCGSFJI-UHFFFAOYSA-N 2,6-difluoro-3-(propylsulfonylamino)benzoic acid Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(O)=O)=C1F RTAWCKGXCGSFJI-UHFFFAOYSA-N 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims 2
- -1 DPEPhos Chemical compound 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims 2
- 150000001450 anions Chemical class 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229910020261 KBF4 Inorganic materials 0.000 claims 1
- 229910021135 KPF6 Inorganic materials 0.000 claims 1
- 229910019398 NaPF6 Inorganic materials 0.000 claims 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims 1
- 229910002666 PdCl2 Inorganic materials 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims 1
- 229910001487 potassium perchlorate Inorganic materials 0.000 claims 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 claims 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 claims 1
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tri(ortho-tolyl)phosphine Substances CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 claims 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (16)
1. Proces za proizvodnju spoja formule (I)
[image]
pri čemu se proces sastoji od
a) izazivanja reakcije između spoja formule (III)
[image]
naznačenog time, što je C1-5 alkil, C3-6 cikloalkil, C3-5 alkenil ili opcionalno supstituirani benzil ili sulfonil ili karbonil i spoja formule (IV) ili spoja formule (VI)
[image]
naznačenog time, što su R2 i R3 grupe prikladne za formiranje Vilsmeierevog reagensa, a A- je odgovarajući nekoordinirajući anion, za dobivanje spoja formule (IX)
[image]
naznačenog time, što je R1 kako je prethodno definirano, i
b) podvrgavanja spoja formule (IX) uklanjanju R1 grupe i konverziji nitrilne grupe u karboksilnu grupu te na kraju obavljanja dekarboksilacije kako bi se dobio spoj formule (X)
[image]
i,
c) izazivanja reakcije između spoja formule (X) i 2,6-difluoro-3-(propilsulfonamido)benzojeve kiseline kako bi se dobio spoj formule (I).
2. Proces prema patentnom zahtjevu 1, naznačen time, što
a) se izaziva reakcija između spoja formule (III)
[image]
naznačenog time, što je R1 C1-5 alkil, C3-6 cikloalkil ili opcionalno supstituirani benzil i spoja formule (IV)
[image]
kako bi se dobio spoj formule (VII)
[image]
naznačen time, što je R1 kako je prethodno definirano, i
b) potom izazivanja reakcije između spoja formule (VII) u prisutnosti paladija kao katalizatora i spoja formule (VIII)
[image]
radi dobivanja spoja formule (IX)
[image]
naznačenog time, što je R1 kako je prethodno definirano, i
c) podvrgavanja spoja formule (IX) uklanjanju R1 grupe i konverziji nitrilne grupe u karboksilnu grupu te na kraju obavljanja dekarboksilacije kako bi se dobio spoj formule (X)
d)
[image]
i,
izazivanja reakcije između spoja formule (X) i 2,6-difluoro-3-(propilsulfonamido)benzojeve kiseline kako bi se dobio spoj formule (I).
3. Proces prema patentnom zahtjevu 1, naznačen time, što
a) se izaziva reakcija između spoja formule (III)
[image]
naznačenog time, što je R1 C1-5 alkil, C3-6 cikloalkil ili opcionalno supstituirani benzil i spoja formule (IV)
[image]
naznačenog time, što su R2 i R3 grupe prikladne za formiranje Vilsmeierevog reagensa, a A- je odgovarajući nekoordinirajući anion, za dobivanje spoja formule (IX)
[image]
naznačenog time, što je R1 kako je prethodno definirano, i
b) podvrgavanja spoja formule (IX) uklanjanju R1 grupe i konverziji nitrilne grupe u karboksilnu grupu te na kraju obavljanja dekarboksilacije kako bi se dobio spoj formule (X)
[image]
i,
c) izazivanja reakcije između spoja formule (X) i 2,6-difluoro-3-(propilsulfonamido)benzojeve kiseline kako bi se dobio spoj formule (I).
4. Proces prema patentnom zahtjevu 2, naznačen time, što se predmetni proces obavlja u prisutnosti katalizatora odabranog iz grupe koja se sastoji od Pd(PPh3)4, Pd(dba)2, Pd2(dba)3, Pd(dppf)Cl2.CH2Cl2, (PPh3)2PdCl2, Pd(OAc)2, PdCl2 ili u kombinaciji s fosfinskim ligandima kao što su PPh3, P(o-tol)3, dppf, dppp, dppe, dppb, PCy3, P(n-Bu)3, P(t-Bu)3, XantPhos, DPEPhos, rac-BINAP i rac-SEGPHOS.
5. Proces prema patentnom zahtjevu 1 ili 3, naznačen time, što su R2 i R3 zasebno metil, etil, izopropil ili zajedno s atomima dušika s kojim su vezani formiraju piperidinski prsten.
6. Proces prema patentnom zahtjevu 5, naznačen time što su R2 i R3 metil.
7. Proces prema patentnom zahtjevu 1 ili 3, naznačen time, što je A- anion soli alkalnog metala odabran iz skupine koja se sastoji od NaPF6, KPF6, KBF4, NaBF4, NaClO4, KClO4.
8. Proces prema patentnom zahtjevu 1 ili 3, naznačen time, što se spoj formule (III)
[image]
priprema izazivanjem reakcije između spoja formule
[image]
i etil-formata i spoja formule R1-NH2, naznačen time, što je R1 C1-5 alkil, C3-6 cikloalkil ili opcionalno supstituirani benzil.
9. Proces prema patentnom zahtjevu 8, naznačen time što je R1 C1-5 alkil.
10. Proces prema patentnom zahtjevu 9, naznačen time što je R1 t-butil.
11. Proces prema patentnom zahtjevu 1, naznačen time, što se spoj formule (VI)
[image]
priprema izazivanjem reakcije između spoja formule (V)
[image]
i spoja formule R2R3NCHO, naznačen time, što su R2 i R3 zasebno metil, etil, izopropil ili zajedno s atomima dušika s kojim su vezani formiraju piperidinski prsten.
12. Proces prema patentnom zahtjevu 11, naznačen time, što su R2 i R3 metil.
13. Proces prema patentnom zahtjevu 10, naznačen time, što se uklanjanje t-butilne grupe obavlja u prisutnosti aluminijevog triklorida (AlCl3) ili pomoću 95-100 % masenog udjela sumporne kiseline.
14. Proces prema patentnom zahtjevu 1 do 3, naznačen time, što se nitrilna grupa spoja formule (IX) pretvara u karboksilnu kiselinu pomoću klorovodične, bromvodične ili sumporne kiseline.
15. Proces prema patentnom zahtjevu od 1 do 3, naznačen time, što dekarboksilacija predstavlja dekarboksilaciju kataliziranu bazom.
16. Proces prema patentnom zahtjevu 15, naznačen time, što se dekarboksilacija katalizirana bazom obavlja pomoću natrijevog hidroksida.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI20165557 | 2016-07-01 | ||
| FI20165778 | 2016-10-12 | ||
| PCT/FI2017/000012 WO2018002415A1 (en) | 2016-07-01 | 2017-06-30 | New processes for the preparation of vemurafenib |
| EP17745368.5A EP3478684B1 (en) | 2016-07-01 | 2017-06-30 | New processes for the preparation of vemurafenib |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20200821T1 true HRP20200821T1 (hr) | 2020-08-07 |
Family
ID=59416718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20200821TT HRP20200821T1 (hr) | 2016-07-01 | 2020-05-21 | Novi procesi za pripremu vemurafeniba |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US10407427B2 (hr) |
| EP (1) | EP3478684B1 (hr) |
| JP (1) | JP6911062B2 (hr) |
| CA (1) | CA3029361A1 (hr) |
| ES (1) | ES2802476T3 (hr) |
| HR (1) | HRP20200821T1 (hr) |
| HU (1) | HUE049682T2 (hr) |
| PL (1) | PL3478684T3 (hr) |
| RS (1) | RS60451B1 (hr) |
| WO (1) | WO2018002415A1 (hr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2018209164B2 (en) | 2017-01-17 | 2021-11-04 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| DK3860598T3 (da) | 2018-10-03 | 2023-10-16 | Jyvaeskylaen Yliopisto | Vemurafenib og salte heraf til anvendelse til behandling af enterovirusinfektioner |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007002433A1 (en) | 2005-06-22 | 2007-01-04 | Plexxikon, Inc. | Pyrrolo [2, 3-b] pyridine derivatives as protein kinase inhibitors |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| US8779150B2 (en) | 2010-07-21 | 2014-07-15 | Hoffmann-La Roche Inc. | Processes for the manufacture of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1 H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide |
| EP2970270A1 (en) | 2013-03-14 | 2016-01-20 | ratiopharm GmbH | Solid state forms of vemurafenib hydrochloride |
| WO2015075749A1 (en) | 2013-11-22 | 2015-05-28 | Laurus Labs Private Limited | Novel processes for the preparation of vemurafenib |
| CZ2013943A3 (cs) | 2013-11-27 | 2015-06-03 | Zentiva, K.S. | Krystalické formy vemurafenibu |
| US10414764B2 (en) | 2014-11-29 | 2019-09-17 | Shilpa Medicare Limited | Substantially pure vemurafenib and its salts |
-
2017
- 2017-06-30 HU HUE17745368A patent/HUE049682T2/hu unknown
- 2017-06-30 US US16/313,597 patent/US10407427B2/en not_active Expired - Fee Related
- 2017-06-30 ES ES17745368T patent/ES2802476T3/es active Active
- 2017-06-30 JP JP2018568670A patent/JP6911062B2/ja active Active
- 2017-06-30 EP EP17745368.5A patent/EP3478684B1/en active Active
- 2017-06-30 WO PCT/FI2017/000012 patent/WO2018002415A1/en unknown
- 2017-06-30 PL PL17745368T patent/PL3478684T3/pl unknown
- 2017-06-30 RS RS20200741A patent/RS60451B1/sr unknown
- 2017-06-30 CA CA3029361A patent/CA3029361A1/en active Pending
-
2020
- 2020-05-21 HR HRP20200821TT patent/HRP20200821T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3029361A1 (en) | 2018-01-04 |
| ES2802476T3 (es) | 2021-01-19 |
| US20190194197A1 (en) | 2019-06-27 |
| WO2018002415A1 (en) | 2018-01-04 |
| EP3478684B1 (en) | 2020-04-15 |
| JP2019522662A (ja) | 2019-08-15 |
| RS60451B1 (sr) | 2020-07-31 |
| EP3478684A1 (en) | 2019-05-08 |
| HUE049682T2 (hu) | 2020-10-28 |
| PL3478684T3 (pl) | 2020-08-10 |
| JP6911062B2 (ja) | 2021-07-28 |
| US10407427B2 (en) | 2019-09-10 |
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