CH617429A5 - - Google Patents
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- CH617429A5 CH617429A5 CH787175A CH787175A CH617429A5 CH 617429 A5 CH617429 A5 CH 617429A5 CH 787175 A CH787175 A CH 787175A CH 787175 A CH787175 A CH 787175A CH 617429 A5 CH617429 A5 CH 617429A5
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- CH
- Switzerland
- Prior art keywords
- radical
- group
- general formula
- compound
- tert
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 118
- 238000006243 chemical reaction Methods 0.000 claims description 38
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 22
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 16
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- YTRGNBTVTHPFJM-UHFFFAOYSA-N pyridazin-3-ylhydrazine Chemical class NNC1=CC=CN=N1 YTRGNBTVTHPFJM-UHFFFAOYSA-N 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- 150000002429 hydrazines Chemical class 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims 6
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
- 125000005336 allyloxy group Chemical group 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 150000007522 mineralic acids Chemical class 0.000 claims 2
- 150000007524 organic acids Chemical class 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 2
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- 102200084471 c.4C>T Human genes 0.000 claims 1
- 230000020176 deacylation Effects 0.000 claims 1
- 238000005947 deacylation reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 139
- 239000000243 solution Substances 0.000 description 120
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 106
- 239000000203 mixture Substances 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- -1 alkanoyl radicals Chemical class 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000002904 solvent Substances 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
- 238000010992 reflux Methods 0.000 description 35
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 32
- 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 31
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 31
- 239000003921 oil Substances 0.000 description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- 150000003254 radicals Chemical class 0.000 description 24
- 238000001953 recrystallisation Methods 0.000 description 23
- 229960000583 acetic acid Drugs 0.000 description 22
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 21
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 20
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 15
- 235000012239 silicon dioxide Nutrition 0.000 description 15
- 239000003480 eluent Substances 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 239000012258 stirred mixture Substances 0.000 description 14
- 238000009835 boiling Methods 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 13
- YQQSRZSUGBETRS-UHFFFAOYSA-N 1h-pyridazine-6-thione Chemical group SC1=CC=CN=N1 YQQSRZSUGBETRS-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 8
- 229940014800 succinic anhydride Drugs 0.000 description 8
- 241001061127 Thione Species 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 7
- 229960003742 phenol Drugs 0.000 description 7
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 6
- QBQVEOIVSWQRDU-UHFFFAOYSA-N 4-(2-hydroxyphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC=C1O QBQVEOIVSWQRDU-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical group OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000006356 dehydrogenation reaction Methods 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 5
- QGONODUKOFNSOY-UHFFFAOYSA-N 1-(tert-butylamino)-3-[2-(6-hydrazinylpyridazin-3-yl)phenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC=CC=C1C1=CC=C(NN)N=N1 QGONODUKOFNSOY-UHFFFAOYSA-N 0.000 description 4
- SYKUIQBLRZSEKK-UHFFFAOYSA-N 1-(tert-butylamino)-3-[3-fluoro-2-(6-hydrazinylpyridazin-3-yl)phenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC=CC(F)=C1C1=CC=C(NN)N=N1 SYKUIQBLRZSEKK-UHFFFAOYSA-N 0.000 description 4
- KYEACNNYFNZCST-UHFFFAOYSA-N 1-methylpyrrolidine-2,5-dione Chemical compound CN1C(=O)CCC1=O KYEACNNYFNZCST-UHFFFAOYSA-N 0.000 description 4
- JTEVRTFFPRBPHQ-UHFFFAOYSA-N 2-(6-chloropyridazin-3-yl)-5-methoxyphenol Chemical compound OC1=CC(OC)=CC=C1C1=CC=C(Cl)N=N1 JTEVRTFFPRBPHQ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- PNZRCNAEMCCREQ-UHFFFAOYSA-N tert-butyl n-[[6-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-4-methoxyphenyl]pyridazin-3-yl]amino]carbamate Chemical compound CC(C)(C)NCC(O)COC1=CC(OC)=CC=C1C1=CC=C(NNC(=O)OC(C)(C)C)N=N1 PNZRCNAEMCCREQ-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000000304 vasodilatating effect Effects 0.000 description 4
- GPBJQFXXNGUQRR-UHFFFAOYSA-N 1-(tert-butylamino)-3-[2-(6-hydrazinylpyridazin-3-yl)-5-methoxyphenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(OC)=CC=C1C1=CC=C(NN)N=N1 GPBJQFXXNGUQRR-UHFFFAOYSA-N 0.000 description 3
- HKMVJOOZSUOYNM-UHFFFAOYSA-N 1-(tert-butylamino)-3-[5-methoxy-2-(6-methoxypyridazin-3-yl)phenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(OC)=CC=C1C1=CC=C(OC)N=N1 HKMVJOOZSUOYNM-UHFFFAOYSA-N 0.000 description 3
- SSDAKJLEKSSAMH-UHFFFAOYSA-N 2,4-dihydro-1h-pyridazin-3-one Chemical compound O=C1CC=CNN1 SSDAKJLEKSSAMH-UHFFFAOYSA-N 0.000 description 3
- UXNQKCOMUCSBSS-UHFFFAOYSA-N 2-phenyl-1,5-dihydropyridazin-6-one Chemical class N1C(=O)CC=CN1C1=CC=CC=C1 UXNQKCOMUCSBSS-UHFFFAOYSA-N 0.000 description 3
- ACTLOQLEUUYVRQ-UHFFFAOYSA-N 3-chloro-4-phenylpyridazine Chemical class ClC1=NN=CC=C1C1=CC=CC=C1 ACTLOQLEUUYVRQ-UHFFFAOYSA-N 0.000 description 3
- KFVDVTYLBHWHHJ-UHFFFAOYSA-N 4-(2-hydroxy-5-nitrophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC([N+]([O-])=O)=CC=C1O KFVDVTYLBHWHHJ-UHFFFAOYSA-N 0.000 description 3
- DDHVIKQPVLQZHU-UHFFFAOYSA-N 4-(6-chloropyridazin-3-yl)benzene-1,3-diol Chemical compound OC1=CC(O)=CC=C1C1=CC=C(Cl)N=N1 DDHVIKQPVLQZHU-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000005695 dehalogenation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 3
- LUASRKNCVQASMW-UHFFFAOYSA-N methyl 4-[2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC=CC=C1OCC1OC1 LUASRKNCVQASMW-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 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 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- AYKYOOPFBCOXSL-UHFFFAOYSA-N (4-hydroxyphenyl)acetonitrile Chemical compound OC1=CC=C(CC#N)C=C1 AYKYOOPFBCOXSL-UHFFFAOYSA-N 0.000 description 2
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
- GJFNRSDCSTVPCJ-UHFFFAOYSA-N 1,8-bis(dimethylamino)naphthalene Chemical compound C1=CC(N(C)C)=C2C(N(C)C)=CC=CC2=C1 GJFNRSDCSTVPCJ-UHFFFAOYSA-N 0.000 description 2
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- KJABEVCIVOHOBS-UHFFFAOYSA-N methyl 4-[5-chloro-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(Cl)=CC=C1OCC1OC1 KJABEVCIVOHOBS-UHFFFAOYSA-N 0.000 description 1
- FCZHDAXPBAHZMH-UHFFFAOYSA-N methyl 4-[5-methoxy-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(OC)=CC=C1OCC1OC1 FCZHDAXPBAHZMH-UHFFFAOYSA-N 0.000 description 1
- MRXAFPLRXZFIKV-UHFFFAOYSA-N methyl 4-[5-methyl-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(C)=CC=C1OCC1OC1 MRXAFPLRXZFIKV-UHFFFAOYSA-N 0.000 description 1
- SRXOJMOGPYFZKC-UHFFFAOYSA-N methyl 4-chloro-4-oxobutanoate Chemical compound COC(=O)CCC(Cl)=O SRXOJMOGPYFZKC-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- DSJYOJYVXXCHHF-UHFFFAOYSA-N n-[3-[3-(tert-butylamino)-2-hydroxypropoxy]-4-(6-hydrazinylpyridazin-3-yl)phenyl]acetamide Chemical compound CC(C)(C)NCC(O)COC1=CC(NC(=O)C)=CC=C1C1=CC=C(NN)N=N1 DSJYOJYVXXCHHF-UHFFFAOYSA-N 0.000 description 1
- VRURQOFXQLLBNT-UHFFFAOYSA-N n-[4-[3-(tert-butylamino)-2-hydroxypropoxy]-3-(6-oxo-4,5-dihydro-1h-pyridazin-3-yl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(C=2CCC(=O)NN=2)=C1 VRURQOFXQLLBNT-UHFFFAOYSA-N 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000011935 selective methylation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ISHLCKAQWKBMAU-UHFFFAOYSA-N tert-butyl n-diazocarbamate Chemical compound CC(C)(C)OC(=O)N=[N+]=[N-] ISHLCKAQWKBMAU-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/12—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/18—Sulfur atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB26864/74A GB1527712A (en) | 1974-06-18 | 1974-06-18 | Hydrazinopyridazines |
| GB2075 | 1975-01-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH617429A5 true CH617429A5 (en, 2012) | 1980-05-30 |
Family
ID=26235616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH787175A CH617429A5 (en, 2012) | 1974-06-18 | 1975-06-17 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4053601A (en, 2012) |
| JP (1) | JPS5113782A (en, 2012) |
| CA (1) | CA1067078A (en, 2012) |
| CH (1) | CH617429A5 (en, 2012) |
| DE (1) | DE2527066A1 (en, 2012) |
| DK (1) | DK145099C (en, 2012) |
| ES (1) | ES438685A1 (en, 2012) |
| FI (1) | FI62532C (en, 2012) |
| FR (1) | FR2275213A1 (en, 2012) |
| IE (1) | IE42214B1 (en, 2012) |
| IL (1) | IL47351A (en, 2012) |
| LU (1) | LU72739A1 (en, 2012) |
| NL (1) | NL7507267A (en, 2012) |
| SE (1) | SE416650B (en, 2012) |
| SU (1) | SU862824A3 (en, 2012) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4314943A (en) * | 1977-07-13 | 1982-02-09 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| US4272440A (en) * | 1978-02-24 | 1981-06-09 | Smithkline Corporation | Intermediates for preparing hydroxyphenylpyridazinones |
| IN148775B (en, 2012) * | 1978-08-04 | 1981-06-13 | Smithkline & French Lab Ltd Uk | |
| US4495352A (en) * | 1979-02-13 | 1985-01-22 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| DE3028453A1 (de) * | 1980-07-26 | 1982-03-18 | Zinser Textilmaschinen Gmbh, 7333 Ebersbach | Spinnmaschine |
| US4340733A (en) * | 1980-09-02 | 1982-07-20 | Smithkline Corporation | Process for preparing 3-chloro-6-(2-hydroxyphenyl)-pyridazines |
| EP0101156A3 (en) * | 1982-06-24 | 1984-08-22 | Smith Kline & French Laboratories Limited | Process for preparing 6-(2-hydroxyphenyl)-3-pyridazinone |
| DE3302442A1 (de) * | 1983-01-26 | 1984-07-26 | Basf Ag, 6700 Ludwigshafen | Neue pyridazinone, verfahren zu ihrer herstellung, diese verbindungen enthaltende therapeutische mittel und deren verwendung |
| GB8323553D0 (en) * | 1983-09-02 | 1983-10-05 | Smith Kline French Lab | Pharmaceutical compositions |
| JPH0629254B2 (ja) * | 1986-09-08 | 1994-04-20 | 帝国臓器製薬株式会社 | ピリダジノン誘導体 |
| EP1461323B1 (en) | 2001-06-12 | 2013-10-09 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2008013838A2 (en) * | 2006-07-25 | 2008-01-31 | Cephalon, Inc. | Pyridizinone derivatives |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| TW202216671A (zh) * | 2020-06-25 | 2022-05-01 | 瑞士商諾華公司 | １，４—二取代的嗒𠯤化合物之製造方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE758146A (fr) * | 1969-10-29 | 1971-04-28 | Smith Kline French Lab | Derives de l'amidine |
| US3818097A (en) * | 1969-10-29 | 1974-06-18 | Smith Kline French Lab | Method of inhibiting histamine activity with isothioureas |
| IT1054107B (it) * | 1970-12-15 | 1981-11-10 | Isf Spa | Nuove 3,idrazinopiridazine 6,sostituite ad attivita antiiperten siva e loro preparazione |
| US3975530A (en) * | 1972-09-05 | 1976-08-17 | Smith Kline & French Laboratories Limited | N-cyano-N'-heterocyclic-alkyl quanidine inhibitors of H2 histamine receptors |
-
1975
- 1975-05-19 IE IE1124/75A patent/IE42214B1/en unknown
- 1975-05-26 IL IL47351A patent/IL47351A/xx unknown
- 1975-05-30 DK DK245275A patent/DK145099C/da not_active IP Right Cessation
- 1975-06-03 US US05/583,379 patent/US4053601A/en not_active Expired - Lifetime
- 1975-06-12 CA CA229,160A patent/CA1067078A/en not_active Expired
- 1975-06-16 FI FI751790A patent/FI62532C/fi not_active IP Right Cessation
- 1975-06-16 LU LU72739A patent/LU72739A1/xx unknown
- 1975-06-17 CH CH787175A patent/CH617429A5/de not_active IP Right Cessation
- 1975-06-17 SE SE7506947A patent/SE416650B/xx unknown
- 1975-06-17 JP JP50074260A patent/JPS5113782A/ja active Pending
- 1975-06-18 FR FR7519034A patent/FR2275213A1/fr active Granted
- 1975-06-18 ES ES438685A patent/ES438685A1/es not_active Expired
- 1975-06-18 NL NL7507267A patent/NL7507267A/xx not_active Application Discontinuation
- 1975-06-18 DE DE19752527066 patent/DE2527066A1/de not_active Ceased
-
1978
- 1978-12-22 SU SU782145553D patent/SU862824A3/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| FR2275213B1 (en, 2012) | 1979-08-10 |
| JPS5113782A (en, 2012) | 1976-02-03 |
| IE42214L (en) | 1975-12-18 |
| FI62532C (fi) | 1983-01-10 |
| DK245275A (da) | 1975-12-19 |
| DK145099B (da) | 1982-08-30 |
| IE42214B1 (en) | 1980-07-02 |
| DE2527066A1 (de) | 1976-01-08 |
| AU8158175A (en) | 1976-12-02 |
| SE416650B (sv) | 1981-01-26 |
| LU72739A1 (en, 2012) | 1975-10-08 |
| SU862824A3 (ru) | 1981-09-07 |
| FI62532B (fi) | 1982-09-30 |
| US4053601A (en) | 1977-10-11 |
| SE7506947L (sv) | 1975-12-19 |
| DK145099C (da) | 1983-01-31 |
| IL47351A0 (en) | 1975-07-28 |
| ES438685A1 (es) | 1977-05-16 |
| NL7507267A (nl) | 1975-12-22 |
| IL47351A (en) | 1980-02-29 |
| FI751790A7 (en, 2012) | 1975-12-19 |
| CA1067078A (en) | 1979-11-27 |
| FR2275213A1 (fr) | 1976-01-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |