DE2424334A1 - Verfahren zur herstellung neuer heterocyclischer verbindungen - Google Patents
Verfahren zur herstellung neuer heterocyclischer verbindungenInfo
- Publication number
- DE2424334A1 DE2424334A1 DE2424334A DE2424334A DE2424334A1 DE 2424334 A1 DE2424334 A1 DE 2424334A1 DE 2424334 A DE2424334 A DE 2424334A DE 2424334 A DE2424334 A DE 2424334A DE 2424334 A1 DE2424334 A1 DE 2424334A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compounds
- triazine
- alkyl
- carbon atoms
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 51
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 127
- 125000000217 alkyl group Chemical group 0.000 claims description 78
- -1 Hydroxy-substituted benzyl group Chemical group 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000004432 carbon atom Chemical group C* 0.000 claims description 44
- 150000002431 hydrogen Chemical group 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 22
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 229940126601 medicinal product Drugs 0.000 claims 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 58
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 27
- 229960001701 chloroform Drugs 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000000203 mixture Substances 0.000 description 22
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 17
- 229960000583 acetic acid Drugs 0.000 description 17
- 238000009835 boiling Methods 0.000 description 16
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000007792 addition Methods 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- 239000012362 glacial acetic acid Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 150000008064 anhydrides Chemical class 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000031709 bromination Effects 0.000 description 5
- 238000005893 bromination reaction Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 3
- JLAPKIOBDCTFEF-UHFFFAOYSA-N 5-aminopyrazole-1-carboximidamide Chemical compound NC(=N)N1N=CC=C1N JLAPKIOBDCTFEF-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- UYJXRRSPUVSSMN-UHFFFAOYSA-P ammonium sulfide Chemical compound [NH4+].[NH4+].[S-2] UYJXRRSPUVSSMN-UHFFFAOYSA-P 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 238000002664 inhalation therapy Methods 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000006396 nitration reaction Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- JUXWUYWPUDKPSD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazine Chemical class N1=CN=CN2N=CC=C21 JUXWUYWPUDKPSD-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- NTAVHHAQSKDWOR-UHFFFAOYSA-N 2,7-dimethyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one Chemical compound CC1=NN2C(=C1)N=C(C)NC2=O NTAVHHAQSKDWOR-UHFFFAOYSA-N 0.000 description 2
- LFCMKGYNGXSZHI-UHFFFAOYSA-N 2-aminoguanidine;dihydrochloride Chemical compound Cl.Cl.NNC(N)=N LFCMKGYNGXSZHI-UHFFFAOYSA-N 0.000 description 2
- UBDZFAGVPPMTIT-UHFFFAOYSA-N 2-aminoguanidine;hydron;chloride Chemical compound [Cl-].NC(N)=N[NH3+] UBDZFAGVPPMTIT-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- HXEKFHWAIWTJQU-UHFFFAOYSA-N 2-methyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one Chemical compound O=C1NC(C)=NC2=CC=NN21 HXEKFHWAIWTJQU-UHFFFAOYSA-N 0.000 description 2
- KMHGYAYOQVLYON-UHFFFAOYSA-N 2-methylpyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound N1=C(C)N=C(N)N2N=CC=C21 KMHGYAYOQVLYON-UHFFFAOYSA-N 0.000 description 2
- FWZQHQXPCCFJOA-UHFFFAOYSA-N 2-methylpyrazolo[1,5-a][1,3,5]triazine Chemical compound N1=C(C)N=CN2N=CC=C21 FWZQHQXPCCFJOA-UHFFFAOYSA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- OBCHBXLOSSHZPP-UHFFFAOYSA-N N=1C=2N(C(=NC=1)S)N=CC=2 Chemical compound N=1C=2N(C(=NC=1)S)N=CC=2 OBCHBXLOSSHZPP-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000005902 aminomethylation reaction Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- ZQWPRMPSCMSAJU-UHFFFAOYSA-N methyl cyclohexanecarboxylate Chemical compound COC(=O)C1CCCCC1 ZQWPRMPSCMSAJU-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 150000002905 orthoesters Chemical class 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- SWGZHHCRMZDRSN-BTJKTKAUSA-N (Z)-but-2-enedioic acid 1-phenoxypropan-2-ylhydrazine Chemical compound OC(=O)\C=C/C(O)=O.NNC(C)COC1=CC=CC=C1 SWGZHHCRMZDRSN-BTJKTKAUSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- WBNTUGPRADFXAL-UHFFFAOYSA-N 1H-pyrazole-5-carboximidamide Chemical compound NC(=N)C=1C=CNN=1 WBNTUGPRADFXAL-UHFFFAOYSA-N 0.000 description 1
- ARIYSXMDTVKAJA-UHFFFAOYSA-N 2-ethylpyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound N1=C(CC)N=C(N)N2N=CC=C21 ARIYSXMDTVKAJA-UHFFFAOYSA-N 0.000 description 1
- CWNRYVQFAMHXLM-UHFFFAOYSA-N 2-formylbutanenitrile Chemical compound CCC(C=O)C#N CWNRYVQFAMHXLM-UHFFFAOYSA-N 0.000 description 1
- IATHTLTVQXMDPC-UHFFFAOYSA-N 2-methyl-3-oxopropanenitrile Chemical compound O=CC(C)C#N IATHTLTVQXMDPC-UHFFFAOYSA-N 0.000 description 1
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- GWLRCPBBLXQXRZ-UHFFFAOYSA-N 3-methylpyrazole-1-carboximidamide Chemical compound CC=1C=CN(C(N)=N)N=1 GWLRCPBBLXQXRZ-UHFFFAOYSA-N 0.000 description 1
- KOYWUYIBEXFRFH-UHFFFAOYSA-N 3-oxopentanenitrile Chemical compound CCC(=O)CC#N KOYWUYIBEXFRFH-UHFFFAOYSA-N 0.000 description 1
- CXEVYNBIUUVCBU-UHFFFAOYSA-N 3-piperidin-1-yl-4-pyrrolidin-1-ylmorpholine Chemical class N1(CCCCC1)C1N(CCOC1)N1CCCC1 CXEVYNBIUUVCBU-UHFFFAOYSA-N 0.000 description 1
- RUSFBHDMYDVOMI-UHFFFAOYSA-N 4-amino-1H-pyrazolo[1,5-a][1,3,5]triazin-2-one Chemical compound Nc1nc(=O)[nH]c2ccnn12 RUSFBHDMYDVOMI-UHFFFAOYSA-N 0.000 description 1
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 1
- HVABAKNGIVLITH-UHFFFAOYSA-N 5-amino-3-ethylpyrazole-1-carboximidamide Chemical compound CCC=1C=C(N)N(C(N)=N)N=1 HVABAKNGIVLITH-UHFFFAOYSA-N 0.000 description 1
- ZNXUEJRLKGFTKF-UHFFFAOYSA-N 5-amino-4-methylpyrazole-1-carboximidamide Chemical compound CC=1C=NN(C(N)=N)C=1N ZNXUEJRLKGFTKF-UHFFFAOYSA-N 0.000 description 1
- AGQOIYCTCOEHGR-UHFFFAOYSA-N 5-methyl-1,2-oxazole Chemical compound CC1=CC=NO1 AGQOIYCTCOEHGR-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000006460 Cyana Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- PEYVWBGHBCDXRT-UHFFFAOYSA-N N1=NNC2=CN=NC2=C1 Chemical group N1=NNC2=CN=NC2=C1 PEYVWBGHBCDXRT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XHXWDFKIXHSRPX-UHFFFAOYSA-N O[ClH]C(Cl)=O Chemical group O[ClH]C(Cl)=O XHXWDFKIXHSRPX-UHFFFAOYSA-N 0.000 description 1
- 208000027771 Obstructive airways disease Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- IMJCZZVIUCMCAP-UHFFFAOYSA-N [Na].C(=O)OCC Chemical compound [Na].C(=O)OCC IMJCZZVIUCMCAP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical class N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 230000000572 bronchospasmolytic effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- YMWUFWXVWZQYCM-UHFFFAOYSA-N chembl439581 Chemical compound C1=C2N=C(C)N=C(O)N2N=C1C1=CC=CC=C1 YMWUFWXVWZQYCM-UHFFFAOYSA-N 0.000 description 1
- 150000001804 chlorine Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical compound NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- NBNBICNWNFQDDD-UHFFFAOYSA-N sulfuryl dibromide Chemical compound BrS(Br)(=O)=O NBNBICNWNFQDDD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004886 thiomorpholines Chemical class 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH725973A CH581137A5 (en) | 1973-05-22 | 1973-05-22 | Pyrazolo(1,5-a)-s-triazines - and their salts, with bronchospasmolytic activity |
| CH725873 | 1973-05-22 | ||
| CH725773 | 1973-05-22 | ||
| CH1694073 | 1973-12-04 | ||
| CH442574 | 1974-03-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2424334A1 true DE2424334A1 (de) | 1974-12-19 |
Family
ID=27509197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2424334A Pending DE2424334A1 (de) | 1973-05-22 | 1974-05-18 | Verfahren zur herstellung neuer heterocyclischer verbindungen |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5019769A (enrdf_load_stackoverflow) |
| AU (1) | AU6925974A (enrdf_load_stackoverflow) |
| DD (1) | DD113907A5 (enrdf_load_stackoverflow) |
| DE (1) | DE2424334A1 (enrdf_load_stackoverflow) |
| FI (1) | FI146174A7 (enrdf_load_stackoverflow) |
| FR (1) | FR2230366A1 (enrdf_load_stackoverflow) |
| IL (1) | IL44873A0 (enrdf_load_stackoverflow) |
| NL (1) | NL7406641A (enrdf_load_stackoverflow) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2900288A1 (de) * | 1978-01-09 | 1979-07-12 | Aron Sa | Aminoderivate von pyrazol eckige klammer auf 1,5-a eckige klammer zu s-triazin, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
| DE3942357A1 (de) * | 1989-12-21 | 1991-06-27 | Boehringer Mannheim Gmbh | 3-aminopyrazolo-heterocyclen, deren verwendung zur bestimmung von wasserstoffperoxid, wasserstoffperoxid-bildenden systemen, peroxidase, peroxidatisch wirksamen substanzen oder von elektronenreichen aromatischen verbindungen, entsprechende bestimmungsverfahren und hierfuer geeignete mittel |
| WO2011141713A1 (en) | 2010-05-13 | 2011-11-17 | Centro Nacional De Investigaciones Oncologicas (Cnio) | New bicyclic compounds as pi3-k and mtor inhibitors |
| US8518931B2 (en) | 2008-04-07 | 2013-08-27 | Irm Llc | Compounds and compositions as kinase inhibitors |
| US9073927B2 (en) | 2010-01-22 | 2015-07-07 | Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii | Inhibitors of PI3 kinase |
| WO2015193169A1 (en) * | 2014-06-17 | 2015-12-23 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as kinase inhibitors |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2842809A1 (fr) * | 2002-07-26 | 2004-01-30 | Greenpharma Sas | NOUVELLES PYRAZOLO[1,5-a]-1,3,5-TRIAZINES SUBSTITUEES ET LEURS ANALOGUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION |
| FR2850653A1 (fr) * | 2003-02-04 | 2004-08-06 | Univ Pasteur | Derives de pyrazolotriazine, procede de preparation et utilisations |
| DE602004018637D1 (de) | 2003-04-09 | 2009-02-05 | Biogen Idec Inc | A2a-adenosinrezeptorantagonisten |
| WO2004092177A1 (en) | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolopyrazines and methods of making and using the same |
| US7285550B2 (en) | 2003-04-09 | 2007-10-23 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines and methods of making and using the same |
| PE20051128A1 (es) * | 2004-02-25 | 2006-01-16 | Schering Corp | Pirazolotriazinas como inhibidores de quinasa |
| JP2018199623A (ja) * | 2015-10-22 | 2018-12-20 | 大正製薬株式会社 | 含窒素縮合複素環化合物 |
| WO2023094310A1 (en) * | 2021-11-23 | 2023-06-01 | Origenis Gmbh | Pyrazolotriazine derivatives useful as cdk9 inhibitors |
-
1974
- 1974-05-17 NL NL7406641A patent/NL7406641A/xx unknown
- 1974-05-18 DE DE2424334A patent/DE2424334A1/de active Pending
- 1974-05-19 FI FI1461/74A patent/FI146174A7/fi unknown
- 1974-05-21 DD DD178657A patent/DD113907A5/xx unknown
- 1974-05-21 JP JP49056179A patent/JPS5019769A/ja active Pending
- 1974-05-21 IL IL44873A patent/IL44873A0/xx unknown
- 1974-05-22 AU AU69259/74A patent/AU6925974A/en not_active Expired
- 1974-05-22 FR FR7417821A patent/FR2230366A1/fr active Granted
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2900288A1 (de) * | 1978-01-09 | 1979-07-12 | Aron Sa | Aminoderivate von pyrazol eckige klammer auf 1,5-a eckige klammer zu s-triazin, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
| DE3942357A1 (de) * | 1989-12-21 | 1991-06-27 | Boehringer Mannheim Gmbh | 3-aminopyrazolo-heterocyclen, deren verwendung zur bestimmung von wasserstoffperoxid, wasserstoffperoxid-bildenden systemen, peroxidase, peroxidatisch wirksamen substanzen oder von elektronenreichen aromatischen verbindungen, entsprechende bestimmungsverfahren und hierfuer geeignete mittel |
| US8518931B2 (en) | 2008-04-07 | 2013-08-27 | Irm Llc | Compounds and compositions as kinase inhibitors |
| US9073927B2 (en) | 2010-01-22 | 2015-07-07 | Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii | Inhibitors of PI3 kinase |
| WO2011141713A1 (en) | 2010-05-13 | 2011-11-17 | Centro Nacional De Investigaciones Oncologicas (Cnio) | New bicyclic compounds as pi3-k and mtor inhibitors |
| WO2015193169A1 (en) * | 2014-06-17 | 2015-12-23 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as kinase inhibitors |
| CN106559992A (zh) * | 2014-06-17 | 2017-04-05 | Ucb生物制药私人有限公司 | 作为激酶抑制剂的稠合的二环杂芳族衍生物 |
| US10000497B2 (en) | 2014-06-17 | 2018-06-19 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as kinase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2230366B1 (enrdf_load_stackoverflow) | 1977-11-10 |
| JPS5019769A (enrdf_load_stackoverflow) | 1975-03-01 |
| NL7406641A (enrdf_load_stackoverflow) | 1974-11-26 |
| FI146174A7 (enrdf_load_stackoverflow) | 1974-11-23 |
| AU6925974A (en) | 1975-11-27 |
| FR2230366A1 (en) | 1974-12-20 |
| DD113907A5 (enrdf_load_stackoverflow) | 1975-07-05 |
| IL44873A0 (en) | 1974-07-31 |
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