DE69911603T2 - Synthese von 5- oder 8-bromoisoquinolin derivaten - Google Patents
Synthese von 5- oder 8-bromoisoquinolin derivaten Download PDFInfo
- Publication number
- DE69911603T2 DE69911603T2 DE69911603T DE69911603T DE69911603T2 DE 69911603 T2 DE69911603 T2 DE 69911603T2 DE 69911603 T DE69911603 T DE 69911603T DE 69911603 T DE69911603 T DE 69911603T DE 69911603 T2 DE69911603 T2 DE 69911603T2
- Authority
- DE
- Germany
- Prior art keywords
- bromoisoquinoline
- catalyst
- hxo
- nitroisoquinoline
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract description 7
- 238000003786 synthesis reaction Methods 0.000 title abstract description 7
- DPRIHFQFWWCIGY-UHFFFAOYSA-N 8-bromoisoquinoline Chemical class C1=NC=C2C(Br)=CC=CC2=C1 DPRIHFQFWWCIGY-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 34
- CYJZJGYYTFQQBY-UHFFFAOYSA-N 5-bromoisoquinoline Chemical compound N1=CC=C2C(Br)=CC=CC2=C1 CYJZJGYYTFQQBY-UHFFFAOYSA-N 0.000 claims abstract description 20
- ULGOLOXWHJEZNZ-UHFFFAOYSA-N 5-bromo-8-nitroisoquinoline Chemical class C1=NC=C2C([N+](=O)[O-])=CC=C(Br)C2=C1 ULGOLOXWHJEZNZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 34
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 12
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 8
- 239000002841 Lewis acid Substances 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 150000007517 lewis acids Chemical class 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- HHBCEKAWSILOOP-UHFFFAOYSA-N 1,3-dibromo-1,3,5-triazinane-2,4,6-trione Chemical compound BrN1C(=O)NC(=O)N(Br)C1=O HHBCEKAWSILOOP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 230000000802 nitrating effect Effects 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 238000005121 nitriding Methods 0.000 claims description 3
- 238000005580 one pot reaction Methods 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 5
- 125000005843 halogen group Chemical group 0.000 claims 3
- VDTUSEIYUROSGJ-UHFFFAOYSA-N 1-nitroisoquinoline Chemical compound C1=CC=C2C([N+](=O)[O-])=NC=CC2=C1 VDTUSEIYUROSGJ-UHFFFAOYSA-N 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- YWWZASFPWWPUBN-UHFFFAOYSA-N 1-bromoisoquinoline Chemical class C1=CC=C2C(Br)=NC=CC2=C1 YWWZASFPWWPUBN-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- 230000031709 bromination Effects 0.000 description 6
- 238000005893 bromination reaction Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- KNBALCRXZUTMBP-UHFFFAOYSA-N 5,8-dibromoisoquinoline Chemical compound N1=CC=C2C(Br)=CC=C(Br)C2=C1 KNBALCRXZUTMBP-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000007605 air drying Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- PYGMPFQCCWBTJQ-UHFFFAOYSA-N 5-nitroisoquinoline Chemical compound N1=CC=C2C([N+](=O)[O-])=CC=CC2=C1 PYGMPFQCCWBTJQ-UHFFFAOYSA-N 0.000 description 2
- BCQCHGICDSWPJK-UHFFFAOYSA-N 8-bromo-5-nitroisoquinoline Chemical compound N1=CC=C2C([N+](=O)[O-])=CC=C(Br)C2=C1 BCQCHGICDSWPJK-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910001960 metal nitrate Inorganic materials 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK88498 | 1998-06-22 | ||
| DKPA199800884 | 1998-06-22 | ||
| PCT/DK1999/000347 WO1999067218A2 (en) | 1998-06-22 | 1999-06-22 | Method of preparing 5- or 8-bromoisoquinoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69911603D1 DE69911603D1 (de) | 2003-10-30 |
| DE69911603T2 true DE69911603T2 (de) | 2004-07-29 |
Family
ID=8098619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69911603T Expired - Lifetime DE69911603T2 (de) | 1998-06-22 | 1999-06-22 | Synthese von 5- oder 8-bromoisoquinolin derivaten |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6500954B1 (enExample) |
| EP (1) | EP1089976B1 (enExample) |
| JP (1) | JP2002518480A (enExample) |
| AT (1) | ATE250584T1 (enExample) |
| AU (1) | AU4498799A (enExample) |
| DE (1) | DE69911603T2 (enExample) |
| DK (1) | DK1089976T3 (enExample) |
| WO (1) | WO1999067218A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040058950A1 (en) * | 2002-07-09 | 2004-03-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors |
| BR0312727A (pt) * | 2002-07-17 | 2005-04-19 | Warner Lambert Co | Combinação de um inibidor alostérico da metaloproteinase-13 de matriz com celecoxib ou valdecoxib |
| US20040092522A1 (en) * | 2002-08-15 | 2004-05-13 | Field Mark John | Synergistic combinations |
| US7419981B2 (en) * | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
| ATE374030T1 (de) * | 2003-07-25 | 2007-10-15 | Hoffmann La Roche | Kombination eines mglur2 antagonists und eines ache inhibitors zur behandlung von akuten und/oder chronischen neurologischen krankheiten |
| WO2005025675A1 (en) * | 2003-09-12 | 2005-03-24 | Pfizer Limited | Combinations comprising alpha-2-delta ligands and serotonin / noradrenaline re-uptake inhibitors |
| GB0322140D0 (en) * | 2003-09-22 | 2003-10-22 | Pfizer Ltd | Combinations |
| DE102005061997A1 (de) * | 2005-12-23 | 2007-07-05 | Basf Ag | Naphthalintetracarbonsäurederivate und deren Verwendung |
| CN113264880B (zh) * | 2021-05-25 | 2022-08-30 | 湖北工业大学 | 一种4-卤代异喹啉化合物的制备方法 |
-
1999
- 1999-06-22 DK DK99927733T patent/DK1089976T3/da active
- 1999-06-22 EP EP99927733A patent/EP1089976B1/en not_active Expired - Lifetime
- 1999-06-22 WO PCT/DK1999/000347 patent/WO1999067218A2/en not_active Ceased
- 1999-06-22 JP JP2000555872A patent/JP2002518480A/ja active Pending
- 1999-06-22 DE DE69911603T patent/DE69911603T2/de not_active Expired - Lifetime
- 1999-06-22 AT AT99927733T patent/ATE250584T1/de not_active IP Right Cessation
- 1999-06-22 AU AU44987/99A patent/AU4498799A/en not_active Abandoned
-
2000
- 2000-10-10 US US09/685,025 patent/US6500954B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69911603D1 (de) | 2003-10-30 |
| JP2002518480A (ja) | 2002-06-25 |
| WO1999067218A3 (en) | 2000-03-16 |
| US6500954B1 (en) | 2002-12-31 |
| EP1089976B1 (en) | 2003-09-24 |
| AU4498799A (en) | 2000-01-10 |
| DK1089976T3 (da) | 2004-01-19 |
| ATE250584T1 (de) | 2003-10-15 |
| WO1999067218A2 (en) | 1999-12-29 |
| EP1089976A1 (en) | 2001-04-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |