HUE030794T2 - Synthesis Processes of Dihydro-Pyrido-Phthalazinone Derivatives - Google Patents
Synthesis Processes of Dihydro-Pyrido-Phthalazinone Derivatives Download PDFInfo
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- HUE030794T2 HUE030794T2 HUE11740513A HUE11740513A HUE030794T2 HU E030794 T2 HUE030794 T2 HU E030794T2 HU E11740513 A HUE11740513 A HU E11740513A HU E11740513 A HUE11740513 A HU E11740513A HU E030794 T2 HUE030794 T2 HU E030794T2
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- methyl
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- 238000000034 method Methods 0.000 title description 45
- 230000008569 process Effects 0.000 title description 10
- 230000002194 synthesizing effect Effects 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 27
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 230000008901 benefit Effects 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims 11
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims 2
- 241000195493 Cryptophyta Species 0.000 claims 1
- 208000003098 Ganglion Cysts Diseases 0.000 claims 1
- 101000713575 Homo sapiens Tubulin beta-3 chain Proteins 0.000 claims 1
- 241001610351 Ipsa Species 0.000 claims 1
- 208000005400 Synovial Cyst Diseases 0.000 claims 1
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- 229910052742 iron Inorganic materials 0.000 claims 1
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- 235000019157 thiamine Nutrition 0.000 claims 1
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- 150000001875 compounds Chemical class 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- 239000012071 phase Substances 0.000 description 40
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- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- 125000000217 alkyl group Chemical group 0.000 description 24
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- 239000003153 chemical reaction reagent Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
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- 239000012442 inert solvent Substances 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- PVAIIDFKUPYMQA-UHFFFAOYSA-N methyl 7-fluoro-2-(4-fluorophenyl)-3-(2-methyl-1,2,4-triazol-3-yl)-4-oxo-2,3-dihydro-1h-quinoline-5-carboxylate Chemical compound O=C1C=2C(C(=O)OC)=CC(F)=CC=2NC(C=2C=CC(F)=CC=2)C1C1=NC=NN1C PVAIIDFKUPYMQA-UHFFFAOYSA-N 0.000 description 14
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- 229910052723 transition metal Inorganic materials 0.000 description 11
- 229910052759 nickel Inorganic materials 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- YTIQTVDMYGLASJ-UHFFFAOYSA-N methyl 5-fluoro-2-[2-(1-methyl-1,2,4-triazol-3-yl)acetyl]-3-nitrobenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC(F)=CC([N+]([O-])=O)=C1C(=O)CC1=NN(C)C=N1 YTIQTVDMYGLASJ-UHFFFAOYSA-N 0.000 description 9
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- 150000003624 transition metals Chemical class 0.000 description 9
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- 238000000926 separation method Methods 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000002841 Lewis acid Substances 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000012661 PARP inhibitor Substances 0.000 description 6
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 6
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 6
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 6
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 6
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- PVAIIDFKUPYMQA-IAGOWNOFSA-N methyl (2s,3s)-7-fluoro-2-(4-fluorophenyl)-3-(2-methyl-1,2,4-triazol-3-yl)-4-oxo-2,3-dihydro-1h-quinoline-5-carboxylate Chemical compound C1([C@@H]2[C@H](NC=3C=C(F)C=C(C=3C2=O)C(=O)OC)C=2C=CC(F)=CC=2)=NC=NN1C PVAIIDFKUPYMQA-IAGOWNOFSA-N 0.000 description 6
- CELADJBVKCWSPO-CHHVJCJISA-N methyl 5-fluoro-2-[(e)-3-(4-fluorophenyl)-2-(2-methyl-1,2,4-triazol-3-yl)prop-2-enoyl]-3-nitrobenzoate Chemical compound COC(=O)C1=CC(F)=CC([N+]([O-])=O)=C1C(=O)C(\C=1N(N=CN=1)C)=C\C1=CC=C(F)C=C1 CELADJBVKCWSPO-CHHVJCJISA-N 0.000 description 6
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- KJRFURLNPVYGNC-UHFFFAOYSA-N methyl 7-fluoro-2-(4-fluorophenyl)-1-hydroxy-3-(2-methyl-1,2,4-triazol-3-yl)-4-oxo-2,3-dihydroquinoline-5-carboxylate Chemical compound O=C1C=2C(C(=O)OC)=CC(F)=CC=2N(O)C(C=2C=CC(F)=CC=2)C1C1=NC=NN1C KJRFURLNPVYGNC-UHFFFAOYSA-N 0.000 description 5
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- NIYWPALNWVTHPJ-UHFFFAOYSA-N methyl 5-fluoro-2-[2-(2-methyl-1,2,4-triazol-3-yl)acetyl]-3-nitrobenzoate Chemical compound COC(=O)C1=CC(F)=CC([N+]([O-])=O)=C1C(=O)CC1=NC=NN1C NIYWPALNWVTHPJ-UHFFFAOYSA-N 0.000 description 4
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- HWGQMRYQVZSGDQ-UHFFFAOYSA-N 7-fluoro-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one Chemical compound CN1N=CN=C1C(C(N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-UHFFFAOYSA-N 0.000 description 3
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- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
-
- 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
- C07D471/06—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30245710P | 2010-02-08 | 2010-02-08 |
Publications (1)
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|---|---|
| HUE030794T2 true HUE030794T2 (en) | 2017-06-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE11740513A HUE030794T2 (en) | 2010-02-08 | 2011-02-08 | Synthesis Processes of Dihydro-Pyrido-Phthalazinone Derivatives |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US8765945B2 (enExample) |
| EP (1) | EP2533640B1 (enExample) |
| JP (1) | JP5735988B2 (enExample) |
| KR (1) | KR101826652B1 (enExample) |
| CN (1) | CN102834008B (enExample) |
| AU (1) | AU2011213584B2 (enExample) |
| BR (1) | BR112012019648B1 (enExample) |
| CA (1) | CA2788114C (enExample) |
| CY (1) | CY1118575T1 (enExample) |
| DK (1) | DK2533640T3 (enExample) |
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