SK18492000A3 - Spôsob prípravy 3(2h)-pyridazinón-4-substituovaných amino-5-chlórderivátov - Google Patents

Spôsob prípravy 3(2h)-pyridazinón-4-substituovaných amino-5-chlórderivátov Download PDF

Info

Publication number: SK18492000A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; group; reacting; reaction
Prior art date: 1998-06-05

Application number

SK1849-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Nagy Pter Ktay

Gyula Simig

Jzsef Barkczy

Ilona Sztruh�R

L�Szl� Balazs

Imre Dom�N

Zoltn Greff

Zolt�N R�Tkai

P�Ter Seres

Tam�S Karancsi

Original Assignee

Egis Gy�Gyszergy�R Rt.

Priority date (The priority date 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 date listed.)

1998-06-05

Filing date

1998-06-05

Publication date

2001-06-11

1998-06-05 Application filed by Egis Gy�Gyszergy�R Rt. filed Critical Egis Gy�Gyszergy�R Rt.

2001-06-11 Publication of SK18492000A3 publication Critical patent/SK18492000A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 37
238000002360 preparation method Methods 0.000 title claims abstract description 8
239000002253 acid Substances 0.000 claims abstract description 24
150000003839 salts Chemical class 0.000 claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 96
238000006243 chemical reaction Methods 0.000 claims description 38
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
FKVPPMFFHJGQIX-UHFFFAOYSA-N 3-[(3,5-dichloropyridazin-4-yl)amino]propan-1-ol Chemical compound OCCCNC1=C(Cl)C=NN=C1Cl FKVPPMFFHJGQIX-UHFFFAOYSA-N 0.000 claims description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
239000003153 chemical reaction reagent Substances 0.000 claims description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
239000011230 binding agent Substances 0.000 claims description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 14
239000000460 chlorine Substances 0.000 claims description 13
-1 benzylsulfonyloxy group Chemical group 0.000 claims description 10
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 9
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
125000001589 carboacyl group Chemical group 0.000 claims description 8
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
239000003513 alkali Substances 0.000 claims description 7
229910000042 hydrogen bromide Inorganic materials 0.000 claims description 7
239000002904 solvent Substances 0.000 claims description 7
HNJWKRMESUMDQE-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-methylethanamine Chemical compound CNCCC1=CC=C(OC)C(OC)=C1 HNJWKRMESUMDQE-UHFFFAOYSA-N 0.000 claims description 6
GBAOOJAWDCNOGO-UHFFFAOYSA-N 3,4,5-trichloropyridazine Chemical compound ClC1=CN=NC(Cl)=C1Cl GBAOOJAWDCNOGO-UHFFFAOYSA-N 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
239000000010 aprotic solvent Substances 0.000 claims description 6
UUMQGMCYAJYYQR-UHFFFAOYSA-N 4-chloro-5-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propylamino]-1h-pyridazin-6-one Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCNC1=C(Cl)C=NNC1=O UUMQGMCYAJYYQR-UHFFFAOYSA-N 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
125000003435 aroyl group Chemical group 0.000 claims description 4
239000001632 sodium acetate Substances 0.000 claims description 4
235000017281 sodium acetate Nutrition 0.000 claims description 4
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
238000000746 purification Methods 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
239000000126 substance Substances 0.000 abstract description 7
230000015572 biosynthetic process Effects 0.000 abstract description 6
238000003786 synthesis reaction Methods 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical group OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
239000012043 crude product Substances 0.000 description 7
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
239000000047 product Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
239000000243 solution Substances 0.000 description 6
238000004458 analytical method Methods 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000012153 distilled water Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
YPJDGPDZLPYDNJ-UHFFFAOYSA-N 5-(3-bromopropylamino)-4-chloro-1h-pyridazin-6-one Chemical compound ClC=1C=NNC(=O)C=1NCCCBr YPJDGPDZLPYDNJ-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
238000009835 boiling Methods 0.000 description 4
150000004649 carbonic acid derivatives Chemical class 0.000 description 4
239000003610 charcoal Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
229960001701 chloroform Drugs 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
239000013078 crystal Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 4
239000012429 reaction media Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
VJWXIRQLLGYIDI-UHFFFAOYSA-N 4,5-dichloro-1h-pyridazin-6-one Chemical compound OC1=NN=CC(Cl)=C1Cl VJWXIRQLLGYIDI-UHFFFAOYSA-N 0.000 description 3
229940040526 anhydrous sodium acetate Drugs 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
150000002484 inorganic compounds Chemical class 0.000 description 3
229910010272 inorganic material Inorganic materials 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
238000003756 stirring Methods 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
JGUMPVKBBFBMAV-UHFFFAOYSA-N 3-[(5,6-dichloropyridazin-4-yl)amino]propan-1-ol Chemical compound OCCCNC1=CN=NC(Cl)=C1Cl JGUMPVKBBFBMAV-UHFFFAOYSA-N 0.000 description 2
229910014033 C-OH Inorganic materials 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
229910014570 C—OH Inorganic materials 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
MMDLBXYSCAXZNC-UHFFFAOYSA-N [C].C1=CC=NN=C1 Chemical group [C].C1=CC=NN=C1 MMDLBXYSCAXZNC-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
238000011109 contamination Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
239000010413 mother solution Substances 0.000 description 2
OAVDWQRDCGTNEK-UHFFFAOYSA-N n,n-diethylethanamine;ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O.CCN(CC)CC OAVDWQRDCGTNEK-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000002894 organic compounds Chemical class 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
206010003658 Atrial Fibrillation Diseases 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
125000006416 CBr Chemical group BrC* 0.000 description 1
MRUZORWXXPXQNC-UHFFFAOYSA-N CNCCC1=CC=C(C)C(C)=C1.CNCCC1=CC=C(OC)C(OC)=C1 Chemical compound CNCCC1=CC=C(C)C(C)=C1.CNCCC1=CC=C(OC)C(OC)=C1 MRUZORWXXPXQNC-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
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 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000003288 anthiarrhythmic effect Effects 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
244000309464 bull Species 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000012994 industrial processing Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000003541 multi-stage reaction Methods 0.000 description 1
ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
XWCCTMBMQUCLSI-UHFFFAOYSA-N n-ethyl-n-propylpropan-1-amine Chemical compound CCCN(CC)CCC XWCCTMBMQUCLSI-UHFFFAOYSA-N 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
208000003663 ventricular fibrillation Diseases 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- 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
- C07D237/20—Nitrogen atoms
- 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
- C07D237/22—Nitrogen and oxygen atoms

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

SK1849-2000A 1998-06-05 1998-06-05 Spôsob prípravy 3(2h)-pyridazinón-4-substituovaných amino-5-chlórderivátov SK18492000A3 (sk)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/HU1998/000054 WO1999064402A1 (en)	1998-06-05	1998-06-05	Process for the preparation of a 3(2h)-pyridazinone- 4-substituted amino- 5-chloro- derivative

Publications (1)

Publication Number	Publication Date
SK18492000A3 true SK18492000A3 (sk)	2001-06-11

Family

ID=10990122

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1849-2000A SK18492000A3 (sk)	1998-06-05	1998-06-05	Spôsob prípravy 3(2h)-pyridazinón-4-substituovaných amino-5-chlórderivátov

Country Status (15)

Country	Link
US (1)	US6800758B1 (de)
EP (1)	EP1082309B1 (de)
JP (1)	JP2004500314A (de)
KR (1)	KR20010052598A (de)
CN (1)	CN1205190C (de)
AT (1)	ATE304535T1 (de)
AU (1)	AU752967B2 (de)
BR (1)	BR9815967A (de)
CA (1)	CA2334220A1 (de)
DE (1)	DE69831612D1 (de)
HK (1)	HK1046529A1 (de)
MX (1)	MXPA00012044A (de)
NO (1)	NO318781B1 (de)
SK (1)	SK18492000A3 (de)
WO (1)	WO1999064402A1 (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HUP0103064A3 (en) *	2001-07-26	2005-06-28	Egis Gyogyszergyar Nyilvanosan	Polymorphic form of 5-chloro-4-(3-{[2-(3,4-dimethoxy-phenyl)-ethyl]-methyl-amino]-propylamino)-3-(2h)-piridazinone fumarate, its use, process for its preparation and pharmaceutical compositions containing it
HU227237B1 (en) *	2001-09-27	2010-12-28	Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag	Substituted alkylpyridazinone derivatives, process for their preparation, pharmaceutical compositions containing them
CN106573893B (zh)	2014-07-31	2020-06-09	巴斯夫欧洲公司	制备吡唑的方法
CA3187499A1 (en)	2015-05-11	2016-11-17	Eric George KLAUBER	Process for preparing 4-amino-pyridazines
WO2018082964A1 (en)	2016-11-04	2018-05-11	Basf Se	Process for the production of pyridazinyl-amides in a one-pot synthesis

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3048487A1 (de)	1980-12-22	1982-07-29	Cassella Ag, 6000 Frankfurt	Basisch substituierte pyridazine, ihre herstellung und ihre verwendung
HU214320B (hu)	1991-12-20	1998-03-02	EGIS Gyógyszergyár Rt.	Eljárás új 3(2H)-piridazinon-származékok és ezeket tartalmazó gyógyszerkészítmények előállítására

1998
- 1998-06-05 AU AU77834/98A patent/AU752967B2/en not_active Ceased
- 1998-06-05 DE DE69831612T patent/DE69831612D1/de not_active Expired - Lifetime
- 1998-06-05 JP JP2000553411A patent/JP2004500314A/ja active Pending
- 1998-06-05 CA CA002334220A patent/CA2334220A1/en not_active Abandoned
- 1998-06-05 CN CNB988141701A patent/CN1205190C/zh not_active Expired - Fee Related
- 1998-06-05 MX MXPA00012044A patent/MXPA00012044A/es unknown
- 1998-06-05 SK SK1849-2000A patent/SK18492000A3/sk unknown
- 1998-06-05 WO PCT/HU1998/000054 patent/WO1999064402A1/en not_active Ceased
- 1998-06-05 KR KR1020007013790A patent/KR20010052598A/ko not_active Abandoned
- 1998-06-05 HK HK02107909.3A patent/HK1046529A1/zh unknown
- 1998-06-05 BR BR9815967-4A patent/BR9815967A/pt not_active IP Right Cessation
- 1998-06-05 US US09/701,732 patent/US6800758B1/en not_active Expired - Fee Related
- 1998-06-05 EP EP98925869A patent/EP1082309B1/de not_active Expired - Lifetime
- 1998-06-05 AT AT98925869T patent/ATE304535T1/de not_active IP Right Cessation
2000
- 2000-12-05 NO NO20006183A patent/NO318781B1/no unknown

Also Published As

Publication number	Publication date
CN1347407A (zh)	2002-05-01
DE69831612D1 (de)	2005-10-20
KR20010052598A (ko)	2001-06-25
CA2334220A1 (en)	1999-12-16
US6800758B1 (en)	2004-10-05
AU752967B2 (en)	2002-10-03
HK1046529A1 (zh)	2003-01-17
MXPA00012044A (es)	2002-04-24
BR9815967A (pt)	2004-06-22
EP1082309A1 (de)	2001-03-14
NO20006183L (no)	2001-01-30
NO20006183D0 (no)	2000-12-05
AU7783498A (en)	1999-12-30
WO1999064402A1 (en)	1999-12-16
NO318781B1 (no)	2005-05-09
ATE304535T1 (de)	2005-09-15
EP1082309B1 (de)	2005-09-14
CN1205190C (zh)	2005-06-08
JP2004500314A (ja)	2004-01-08

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CA1271751A (en)	1990-07-17	Dihydroimidazo[1,2-a]pyrimidine derivatives
JP2860689B2 (ja)	1999-02-24	ピリミジン誘導体
SK18492000A3 (sk)	2001-06-11	Spôsob prípravy 3(2h)-pyridazinón-4-substituovaných amino-5-chlórderivátov
US4826845A (en)	1989-05-02	3(2H)-pyridazinones and pharmaceutical compositions thereof
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FR2616433A1 (fr)	1988-12-16	Nouveaux derives piperazinyl alkyl piperazine, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
US4180578A (en)	1979-12-25	2,4-Diamino-5-(4'-methylthio)benzylpyrimidenes, compounds, compositions and method of use
US4281125A (en)	1981-07-28	Quinoline catalyzed synthesis of pyridazinone pharmaceutical intermediates
US20030069423A1 (en)	2003-04-10	Novel processes for the preparation of adenosine compounds and intermediates thereto
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SK131193A3 (en)	1994-12-07	Heterocyclic compounds with antiasthmatic/antialergic, antiinflammatic positive inotropic and blood pressure lowering effect
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