NO140011B - 6-substituerte-4-halogen-1,2-dihydro-1-hydroxy-2-iminopyrimidiner for anvendelse ved fremstilling av de tilsvarende 4-aminoforbindelser - Google Patents
6-substituerte-4-halogen-1,2-dihydro-1-hydroxy-2-iminopyrimidiner for anvendelse ved fremstilling av de tilsvarende 4-aminoforbindelser Download PDFInfo
- Publication number
- NO140011B NO140011B NO741201A NO741201A NO140011B NO 140011 B NO140011 B NO 140011B NO 741201 A NO741201 A NO 741201A NO 741201 A NO741201 A NO 741201A NO 140011 B NO140011 B NO 140011B
- Authority
- NO
- Norway
- Prior art keywords
- acid
- dihydro
- hydroxy
- substituted
- carbon atoms
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 title description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- 239000002253 acid Substances 0.000 description 9
- -1 6-substituted-4-amino-1,2-dihydro-1-hydroxy-2-iminopyrimidines Chemical class 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- VBNFLOFWLGPGJE-UHFFFAOYSA-N 4-chloro-1-hydroxy-6-methylpyrimidin-2-imine Chemical compound CC1=CC(Cl)=NC(=N)N1O VBNFLOFWLGPGJE-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 150000004965 peroxy acids Chemical class 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- DOYINGSIUJRVKA-UHFFFAOYSA-N 6-chloro-3-hydroxy-2-iminopyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC(=N)N1O DOYINGSIUJRVKA-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ASIQPGWXHHXHEX-UHFFFAOYSA-N 1-hydroxy-6-methyl-4-pyrrolidin-1-ylpyrimidin-2-imine Chemical compound N=C1N(O)C(C)=CC(N2CCCC2)=N1 ASIQPGWXHHXHEX-UHFFFAOYSA-N 0.000 description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- ZIMGGGWCDYVHOY-UHFFFAOYSA-N 3-hydroxy-2-imino-6-(1-piperidinyl)-4-pyrimidinamine Chemical compound N=C1N(O)C(N)=CC(N2CCCCC2)=N1 ZIMGGGWCDYVHOY-UHFFFAOYSA-N 0.000 description 2
- 150000005007 4-aminopyrimidines Chemical class 0.000 description 2
- QJIUMVUZDYPQRT-UHFFFAOYSA-N 6-chloro-2,4-pyrimidinediamine Chemical compound NC1=CC(Cl)=NC(N)=N1 QJIUMVUZDYPQRT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000004069 aziridinyl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- ROBFUDYVXSDBQM-UHFFFAOYSA-N hydroxymalonic acid Chemical compound OC(=O)C(O)C(O)=O ROBFUDYVXSDBQM-UHFFFAOYSA-N 0.000 description 2
- 125000001326 naphthylalkyl group Chemical group 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ADZCGFWMBYZOJD-UHFFFAOYSA-N 2,3,4,5,6-pentamethylbenzenecarboperoxoic acid Chemical compound CC1=C(C)C(C)=C(C(=O)OO)C(C)=C1C ADZCGFWMBYZOJD-UHFFFAOYSA-N 0.000 description 1
- DLGDBMOKNCDIBH-UHFFFAOYSA-N 2,3,4,6-tetrachlorobenzenecarboperoxoic acid Chemical compound ClC1=C(C(=CC(=C1C(=O)OO)Cl)Cl)Cl DLGDBMOKNCDIBH-UHFFFAOYSA-N 0.000 description 1
- RBRBLJFOKNCFRR-UHFFFAOYSA-N 2,4-dinitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O RBRBLJFOKNCFRR-UHFFFAOYSA-N 0.000 description 1
- NPTGVVKPLWFPPX-UHFFFAOYSA-N 2-amino-4-chloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(N)=N1 NPTGVVKPLWFPPX-UHFFFAOYSA-N 0.000 description 1
- BUJMXKLCCKQCGA-UHFFFAOYSA-N 2-bromobenzenecarboperoxoic acid Chemical class OOC(=O)C1=CC=CC=C1Br BUJMXKLCCKQCGA-UHFFFAOYSA-N 0.000 description 1
- QDACQOOLIVCDNP-UHFFFAOYSA-N 2-nitro-1-oxidopyridin-1-ium Chemical class [O-][N+](=O)C1=CC=CC=[N+]1[O-] QDACQOOLIVCDNP-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical class [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- HPLBJCPAWPQKDU-UHFFFAOYSA-N 3,4-dimethylbenzenecarboperoxoic acid Chemical compound CC1=CC(=CC=C1C)C(=O)OO HPLBJCPAWPQKDU-UHFFFAOYSA-N 0.000 description 1
- ULVUGRJTZCWZRN-UHFFFAOYSA-N 3,5-dichlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC(Cl)=CC(Cl)=C1 ULVUGRJTZCWZRN-UHFFFAOYSA-N 0.000 description 1
- AFYRKIAHDASULF-UHFFFAOYSA-N 3-chloro-4-methoxybenzenecarboperoxoic acid Chemical compound ClC1=CC(=CC=C1OC)C(=O)OO AFYRKIAHDASULF-UHFFFAOYSA-N 0.000 description 1
- GGLCWCJIZADWQY-UHFFFAOYSA-N 3-chloro-4-nitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC(Cl)=C(C=C1)[N+]([O-])=O GGLCWCJIZADWQY-UHFFFAOYSA-N 0.000 description 1
- OQOXQGCYFYSFRH-UHFFFAOYSA-N 3-nitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC([N+]([O-])=O)=C1 OQOXQGCYFYSFRH-UHFFFAOYSA-N 0.000 description 1
- WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
- AQBWIEDDMPCUFT-UHFFFAOYSA-N 4-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=C(C(O)=O)C=C1 AQBWIEDDMPCUFT-UHFFFAOYSA-N 0.000 description 1
- IAPQCQCJCOIPGG-UHFFFAOYSA-N 4-methoxybenzenecarboperoxoic acid Chemical compound COC1=CC=C(C(=O)OO)C=C1 IAPQCQCJCOIPGG-UHFFFAOYSA-N 0.000 description 1
- IFDPVSBDNAQBRQ-UHFFFAOYSA-N 4-methylbenzenecarboperoxoic acid Chemical compound CC1=CC=C(C(=O)OO)C=C1 IFDPVSBDNAQBRQ-UHFFFAOYSA-N 0.000 description 1
- IMKINJYINPIXRW-UHFFFAOYSA-N 4-phenoxypyrimidine Chemical compound C=1C=NC=NC=1OC1=CC=CC=C1 IMKINJYINPIXRW-UHFFFAOYSA-N 0.000 description 1
- WOTPTUYHTAPCBA-UHFFFAOYSA-N 6-bromo-3-hydroxy-2-iminopyrimidin-4-amine Chemical compound NC1=CC(Br)=NC(=N)N1O WOTPTUYHTAPCBA-UHFFFAOYSA-N 0.000 description 1
- ULSYPLOIMKLSCA-UHFFFAOYSA-N 6-bromopyrimidine-2,4-diamine Chemical compound NC1=CC(Br)=NC(N)=N1 ULSYPLOIMKLSCA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101100167280 Caenorhabditis elegans cin-4 gene Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- NNDASDMUUQRZKG-UHFFFAOYSA-N NC1=CC=CC=[N+]1[O-] Chemical class NC1=CC=CC=[N+]1[O-] NNDASDMUUQRZKG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 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
- 239000000370 acceptor Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols 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
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Solid-Phase Diffusion Into Metallic Material Surfaces (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
6-substituerte-4-halogen-l,2-dihydro-l-hydroxy-2-iminiopyrimidiner for anvendelse ved fremstilling av de tilsvarende 4-aminoforbindelser.
Description
Foreliggende oppfinnelse angår hittil ukjente 6-substitu-erte-4-halogen-l,2-dihydro-l-hydroxy-2-iminopyrimidiner av formelen
.hvor R, er alkyl med 1-8 carbonatomer eller NH2, og X er brom'
eller klor. De nye forbindelser er viktige mellomprodukter ved fremstilling av hypertensivt aktive 6-substituerte-4-amino-l,2-dihydro-l-hydroxy-2-iminopyrimidiner.
De nye 6-substituerte-4-halogen-l,2-dihydro-l-hydroxy-2-iminopyrimidiner har ganske overraskende vist seg å dannes ved oxydasjon av 6-substituerte-4-halogenpyrimidiner med persyrer;
og utmerker seg ved å være uventet stabile i nærvær av persyre-oxydasjonsmidler. Analoge aminopyridin-N-oxyder har ikke tidlig-
ere kunnet isoleres fra persyre-reaksjonsblandinger, idet amino-pyridiner, hvilket fremgår fra Taylor og Driscoll, J. Org. Chem.
25, 1716 (1960), bare gir nitropyridiner og nitropyridin-N-oxyder.
Andre forsøk har vist at heller ikke aminosubstituerte klortria-zin-N-oxyder kan isoleres fra persyrereaksjonsblandinger.
De nye 6-substituerte-4-halogen-l,2-dihydro-l-hydroxy-2-iminopyrimidiner (II) gjør det mulig å fremstille de tilsvarende 4-aminopyrimidiner på en langt bedre og enklere måte enn den tid-
ligere kjente som er beskrevet i US patentskrift nr. 3 4 61 4 61.
Ifølge den kjente fremgangsmåte kreves et 4-fenoxypyrimidin-mellompro-dukt som oxyderes til N-oxydet, som deretter må omsettes med et amin for utbytting av fenoxygruppen. Ved anvendelse av de foreliggende 4-halogen-N-oxyder, som det altså overraskende har vist seg mulig å isolere, blir følgelig fremstillingen av 4-aminopyrimidiner vesentlig forenklet, idet ett av trinnene kan ute-lates .
Den fremgangsmåte hvori forbindelsene ifølge oppfinnelsen inngår kan illustreres av følgende reaksjonsskjerna: hvor R er -NH2 eller alkyl med fra 1- 8 carbonatomer, X er brom eller klor og R1 er en del valgt fra gruppen bestående av (a) grupper av den generelle formel:
hvor R2 og R3 er hydrogen, alkyl med fra 1-8 carbonatomer, alkenyl med fra 1-8 carbonatomer, usubstituert og alkylsubsti-
tuert cycloalkyl med fra 3-10 carbonatomer, fenylalkyl med fra. 7-12 carbonatomer, nafthvlalkyl med fra 11 - 14 carbonatomer, med det forbehold at ikke både R2 og R3 er hydrogen og (b) de heterocycliske deler aziridinyl, azetidinyl, pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino, octamethylenimino, morfolino, 4-alkylpiperazinyl, idet hver av de nevnte heterocycliske deler har som substituenter på carbonatomene bundet fra null til 3 alkylgrupper, hvor alkylgruppene, som er knyttet til de heterocycliske deler har fra 1-8 carbonatomer.
De nye 1,2-dihydro-4-halogen-l-hydroxypyrimidiner (II) ifølge oppfinnelsen kan representeres også ved andre formler enn formel II. Forbindelser av formlene IIA er tautomere med forbindelsene av formlene II. Det skal imidlertid forståes at de nye forbindelser, II sannsynligvis er blandinger av tautomere former, hvis sammensetning er avhengig av slike faktorer som formen av R og X og omgivelsene. I enkelte tilfeller kan den ene eller den annen form være dominerende.
De nye mellomprodukter av formel II er aminer, og fore-ligger i den ikke-protoniserte form eller som fri base, eller i den protoniserte form eller som syreaddisjonssalt, avhengig av pH på omgivelsene.De danner stabile protoniserte forbindelser, dvs. syreaddisjonssalter av mono- eller dibasisk syre, ved nøytrali-sasjon med egnede syrer, f.eks. saltsyre, hydrogenbromid, svovel-syre, fosforsyre, salpetersyre, eddiksyre, benzoesyre, salicylsyre, glycolsyre, ravsyre, nicotinsyre, tartronsyre, maleinsyre, eple-syre, pamoinsyre (pamoic acid), methansulfonsyre, cyclohexansulfam-syre, picrinsyre, melkesyrene og lignende. Disse syreaddisjonssalter er anvendbare til forbedring eller rensing av de fri baser. De fri baser er anvendbare som syreakseptorer ved nøytralisering av uønsket syre eller ved å absorbere en syre når den dannes i en kjemisk reakjson, f.eks. en dehydrohalogeneringsreaksjon hvor hydrogen og klor, brom eller jod fjernes fra tilstøtende carbonatomer .
De nye forbindelser av formel II danner salter med fluorsil-iciumsyre, som er anvendbare som møllsikre midler ifølge US pa-tenter 1.915.334 og 2.075.359. De danner også salter med thio-cyansyre som kondenseres med formaldehyd og danner faste materialer som er anvendbare som beiseinhibitorer ifølge US patentene 2.425.320 og 2.606.155.
Trinn 1 i fremgangsmåten ifølge ovenfor omtalte skjema innbefatter oxydering av et 6-substituert-4-halogenpyrimidin I med en persyre under dannelse av 6-substituert-4- halogeri-1,2-dihydro-l-hydroxy-2-iminopyrimidin II. Trinn 2 beskriver anvendelsen av mel-lomproduktet med formel II og innbefatter omsetning av forbindelsene II med det egnede amin under dannelse av 6-substituert-4-amino-l,2-dihydro-l-hydroxy-2-iminopyrimidiner (III).
Trinn 1 kan utføres ved en temperatur på -10 til 100°C, helst ved en temperatur på 0 til 25°C, og molforholdet mellom perbenzoe-syren og forbindelse 1 er 5 til 1, helst 1,5 til 1.
Egnede løsningsmidler er alkoholer, slike som methanol, etha-nol, isopropanol, glycol og propylenglycol, ethere, slike som di-ethylether, methylcellosolvfi, ethylenglycol, og ethylenglycol-di-methylether, klorinerte hydrocarboner; slike som kloroform, carbon-tetraklorid, og ethylendiklorid, hydrocarboner; slike som hexan, cyclohexan, benzen, toluen, xylén og nafthalen, ketoner; slike som aceton og methylethylketon, amider, slike som dimethylformamid og dimethylacetamid; og andre polare løsningsmidler slike som dime-thylsulfoxyd og dimethylsulfon. Blandinger av de ovenfor angitte løsningsmidler kan også benyttes.
Egnede oxydasjonsmidler for dette trinn innbefatter perbenzoe-syre. 0-, m-, p-klor- og bromperbenzoesyrer, 3,5-diklorperbenzoe-syre, 2,3,4,6-tetraklorperbenzoesyre, 4-methylperbenzoesyre, penta-methylperbenzoesyre, 3,4-dimethylperbenzoesyre, 0-, m-, og p-methoxy-perbenzoesyre, 3-nitroperbenzoezyre, 2,4-dinitroperbenzoesyre, 3-klor-4-methoxyperbenzoesyre, 3-klor-4-nitroperbenzoesyre og 0-,
m-, p-carboxyperbenzoesyre.
De 6-substituerte-4-halogenpyrimidiner av formel I som an-vendes i trinn 1 er kjent innen faget eller kan fremstilles ved kjente metoder innen faget. Se f.eks. US patent 3.461.461, spalte 6, linjer 16-75 og spalte 7, linjer 1-8 og Braker et al., J. Amer. Chem. Soc, 69.3072 (1947).
I trinn 2 beskrives anvendelsen av mellomproduktene 6-substi-tuerte 4-halogen-l,2-dihydro-l-hydroxy-2-iminopyrimidin II som ble dannet i trinn 1, og består i å omsette et amin med den generelle formel hvor R2 og R, har de ovenfor angitte betydninger med forbindelsene av formel II. Molforholdet mellom aminet og forbindelsen av II er 100 til 1, helst 20 til 1. Reaksjonstemperaturen kan være innen området fra 0-200°C, fordelaktig fra 50° - 150°C. I dette trinn kan enten aminet
hvor R2 og R^ er som ovenfor angitt, eller et hvilket som helst av de i trinn 1 benyttede løsningsmidler, benyttes som løsnings-middel .
Følgende eksempler illustrerer oppfinnelsen.
Eksempel 1
6-amino-4-klor-l,2-dihydro-l-hydroxy-2-iminopyrimidin
30 g (0,15 mol) 4-klor-2,6-diaminopyrimidin ble løst i
600 ml varm alkohol, løsningen avkjølt til 0-10°C, og 41,8 g (0,24 mol) m-klorperbenzoesyre ble tilsatt. Blandingen ble holdt ved 0-10°C i 4 timer og filtrert. Det faste stoff ble ristet i 2 timer i 0,24 mol 10 %-ig natriumhydroxyd og filtrert. Det faste stoff ble vasket med vann og tørket og ga 19,3 g urent produkt. Dette produkt ble ekstrahert i 1 time med 900 ml kokende acetonitril som ga 14,8 g (44,7 % utbytte) av 6-amino-4-klor-l,2-dihydro-l-hydroxy-2-iminopyrimidin, sm.p. 193°C.
Analyse
Beregnet for C4H5CIN40: C 29,93; H 3,14; Cl 22,09;
N 34,90
Funnet : C 30,60; H 3,43; Cl 22,26;
N 34,41
Ved å benytte den angitte fremgangsmåte men erstatte 4-klor-2,6-diaminopyrimidin med 4-brom-2,6-diaminopyrimidin erholdt man 6-amino-4-brom-l,2-dihydro-l-hydroxy-2-iminopyrimidin.
Sluttproduktet
6-amino-l,2-dihydro-l-hydroxy-2-imino-4-piperidinopyrimidin fremstilles som følger: En blanding av 3,0 g (0,019 mol) 6-amino-4-klor-l,2-dihydro-l-hydroxy-2-iminopyrimidin (Eksempel 1) og 35 ml piperidin ble kokt under tilbakeløp i 1,5 timer, kjølt og filtrert. Det faste stoff ble ristet i 20 minutter i en løsning av 0,8 g natriumhydroxyd i 30 ml vann og filtrert. Det faste stoff ble vasket med vann og ekstrahert med 800 ml kokende acetonitril og filtrert, og ga 3,5 g (89 % utbytte) av 6-amino-l,2-dihydro-l-hydroxy-2-imino-4-piperidino-pyrimidin, sm.p. 248°C, spaltning ved 259-261°C.
Analyse
Beregnet for CgH15N50: C 51,66; H 7,22; N 33,47
Funnet: C 51,94; H 6,87; N 33,36
Eksempel 2
4-klor-l,2-dihydro-l-hydroxy-2-imino-6-methyl-pyrimidin
En blanding av 30 g (0,208 mol) 2-amino-4-klor-6-methyl-pyrimidin og 800 ml alkohol ble kokt under tilbakeløp inntil det ble dannet en klar løsning. Løsningen ble avkjølt til 5°C og 40 g (0,23 mol) m-klorperbenzoesyre ble tilsatt. Blandingen ble omrørt ved 0-10°C i 4 timer og filtrert. Filtratet ble tillatt å stå i 20 timer og filtrert. Det faste stoff fra dette siste filtreringstrinn ble rekrystallisert fra acetonitril og ga 2,6 g 4-klor-l,2-dihydro-l-hydroxy-2-imino-6-methylpyrimidin, sm.p. hurtig spaltning ved 161°C.
Analyse
Beregnet for C5HgCIN30: C 37,63; H 3,79; Cl 22,22;
N 26,33
Funnet: C 37,64; H 4,09; Cl 23,20;
N 26,11
Sluttproduktet
1,2-dihydro-.l-hydroxy-2-imino—6-methyl-4-pyrrolidylpyrimidin ble fremstilt som følger: En blanding av 10,0 g (0.062 mol) 4-klor-l,2-dihydro-l-hydroxy-2-imino-6-methylpyrimidin (Eksempel 1) og 70 ml pyrrolidin ble kokt under tilbakeløp i to timer, kjølt og filtrert.
Det faste stoff ble vasket henholdsvis med pyrrolidin og ether
og deretter ekstrahert med 300 ml acetonitril som ga 9,5 g (82 %)
1,2-dihydro-l-hydroxy-2-imino-6-methyl-4-pyrrolidylpyrimidin, sm.p. 271-273°C.
Analyse
Beregnet for CgH^NjO: C 55,65; H 7,26; N 28,84 ; 0 8,24;
Funnet : C 55,27; H 7,19; N 28,07; 0 6,59.
6-substituerte-4-halogen-l,2-dihydro-l-hydroxy-2-imino-pyrimidiner for anvendelse ved fremstilling av terapeutisk aktive 4-aminoforbindelser med formelen
hvor R er -NH2 eller alkyl med 1-8" carbonatomer, R^ er
a) en molekyldel med generell formel:
hvor R2 og R^ er hydrogen, alkyl med 1-8 carbonatomer, alkenyl
med 1-8 carbonatomer, usubstituert og alkylsubstituert cyclo-
alkyl med 3-10 carbonatomer, fenylalkyl med 7-12 carbonatomer eller nafthylalkyl med 11 - 14 carbonatomer, med det forbehold at ikke både R2 og R- er hydrogen, eller
b) en heterocyclisk gruppe omfattende aziridinyl, azetidinyl, pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino, octamethylenimino, morfolino, 4-alkyl-piperazinyl, idet hver av de nevnte heterocycliske grupper har som substituenter på carbon-atomene bundet 0-3 alkylgrupper, hvor alkylgruppene bundet til de heterocycliske grupper har fra 1 til 8 carbonatomer, karakterisert ved at de har generell formel:
hvor R er -NH2 eller alkyl med 1-8 carbonatomer, og X er brom eller klor.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2435170A | 1970-03-31 | 1970-03-31 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO741201L NO741201L (no) | 1971-10-01 |
NO140011B true NO140011B (no) | 1979-03-12 |
NO140011C NO140011C (no) | 1979-06-20 |
Family
ID=21820134
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO1160/71A NO131420C (no) | 1970-03-31 | 1971-03-29 | |
NO741201A NO140011C (no) | 1970-03-31 | 1974-04-03 | 6-substituerte-4-halogen-1,2-dihydro-1-hydroxy-2-iminopyrimidiner for anvendelse ved fremstilling av de tilsvarende 4-aminoforbindelser |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO1160/71A NO131420C (no) | 1970-03-31 | 1971-03-29 |
Country Status (10)
Country | Link |
---|---|
US (1) | US3644364A (no) |
JP (1) | JPS551259B1 (no) |
CH (1) | CH551979A (no) |
DE (1) | DE2114887C3 (no) |
DK (2) | DK128116B (no) |
FI (1) | FI55194C (no) |
FR (1) | FR2087936A5 (no) |
NL (1) | NL7104019A (no) |
NO (2) | NO131420C (no) |
SE (2) | SE384504B (no) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3931181A (en) * | 1973-07-27 | 1976-01-06 | Hoffmann-La Roche Inc. | 2,4-Diamino-5-benzylpyrimidines |
US4013778A (en) * | 1974-08-05 | 1977-03-22 | Warner-Lambert Company | Method for reducing blood pressure |
US4175189A (en) * | 1977-02-04 | 1979-11-20 | Hoffmann-La Roche Inc. | 6-Chloro-2,4-pyrimidine-dicarbamate-3-oxides |
US4175190A (en) * | 1977-02-04 | 1979-11-20 | Hoffmann-La Roche Inc. | 6-Chloro-2,4-pyrimidine-dicarbamate-3-oxides |
US5196533A (en) * | 1983-04-11 | 1993-03-23 | South Alabama Medical Science Foundation, Usa | Cyclization of 5 amino-pyrimidines to quinoid 6,6 disubstituted dihydropteridines |
HU196067B (en) * | 1986-07-10 | 1988-09-28 | Richter Gedeon Vegyeszet | Process for production of 6-amin-1,2-dihydro-1-hydroxi-2-imino-4-piperidin-piramidin |
FI864046A (fi) * | 1986-10-07 | 1988-04-08 | Farmos Oy | Foerfarande foer framstaellning av en terapeutiskt aktiv foerening. |
US6465514B1 (en) | 1986-12-29 | 2002-10-15 | Kenneth M. Hallam | Methods and compositions for the promotion of hair growth |
US4927626A (en) * | 1988-10-28 | 1990-05-22 | Devillez Richard L | Method for enhancement of unguis growth |
US4959475A (en) * | 1989-01-04 | 1990-09-25 | Lonza Ltd. | Process for the production of 2,4-diamino-6-piperidinyl-pyrimidine-3-N-oxide |
FR2651122B1 (fr) * | 1989-08-29 | 1994-10-28 | Oreal | Compositions destinees a etre utilisees pour freiner la chute des cheveux et pour induire et stimuler leur croissance, contenant des derives de l'amino-2 pyrimidine oxyde-3 et nouveaux composes derives de l'amino-2 pyrimidine oxyde-3. |
DE69108402T2 (de) * | 1990-11-14 | 1995-10-05 | Upjohn Co | 5-fluor-2,4,6-pyrimidinthiaminderivate zur verhinderung des haarsausfalls. |
US5502050A (en) * | 1993-11-29 | 1996-03-26 | Cornell Research Foundation, Inc. | Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis |
FR2753378B1 (fr) * | 1996-09-17 | 1998-11-20 | Oreal | Utilisation dans une composition en tant que stimulateur de tyrosinase d'au moins un derive de pyrimidine 3-oxyde, substitue en 6 |
US20050163811A1 (en) * | 2004-01-23 | 2005-07-28 | Richard Lee | Topical solutions comprising high concentrations of piperidinopyrimidine derivatives and methods of use thereof |
EP2730271B1 (en) | 2012-11-11 | 2018-01-24 | Symrise AG | Aqeuous compositions |
CN107129470A (zh) * | 2017-06-12 | 2017-09-05 | 常州市天华制药有限公司 | 一种米诺地尔的合成与精制方法 |
CN107235919B (zh) * | 2017-06-22 | 2020-05-12 | 安徽拜善晟制药有限公司 | 一种米诺地尔的合成工艺 |
CN114213340B (zh) | 2022-02-22 | 2022-06-07 | 北京蓝晶微生物科技有限公司 | 2,4-二氨基嘧啶氧化物的制备方法 |
CN115572265A (zh) * | 2022-10-10 | 2023-01-06 | 江苏海悦康医药科技有限公司 | 一种高纯度米诺地尔的绿色合成工艺 |
-
1970
- 1970-03-31 US US24351A patent/US3644364A/en not_active Expired - Lifetime
-
1971
- 1971-03-04 CH CH314471A patent/CH551979A/xx not_active IP Right Cessation
- 1971-03-04 JP JP1103771A patent/JPS551259B1/ja active Pending
- 1971-03-17 DK DK128571AA patent/DK128116B/da not_active IP Right Cessation
- 1971-03-23 FI FI828/71A patent/FI55194C/fi active
- 1971-03-25 NL NL7104019A patent/NL7104019A/xx unknown
- 1971-03-26 SE SE7317494A patent/SE384504B/xx unknown
- 1971-03-26 SE SE7103975A patent/SE384368B/xx unknown
- 1971-03-27 DE DE2114887A patent/DE2114887C3/de not_active Expired
- 1971-03-29 NO NO1160/71A patent/NO131420C/no unknown
- 1971-03-30 FR FR7111170A patent/FR2087936A5/fr not_active Expired
- 1971-11-17 DK DK564671AA patent/DK128539B/da not_active IP Right Cessation
-
1974
- 1974-04-03 NO NO741201A patent/NO140011C/no unknown
Also Published As
Publication number | Publication date |
---|---|
US3644364A (en) | 1972-02-22 |
DE2114887A1 (de) | 1971-10-14 |
DE2114887C3 (de) | 1980-09-11 |
FI55194C (fi) | 1981-05-18 |
NO741201L (no) | 1971-10-01 |
NO140011C (no) | 1979-06-20 |
FI55194B (fi) | 1979-02-28 |
CH551979A (de) | 1974-07-31 |
DK128539B (da) | 1974-05-20 |
NL7104019A (no) | 1971-10-04 |
SE384504B (sv) | 1976-05-10 |
JPS551259B1 (no) | 1980-01-12 |
FR2087936A5 (no) | 1971-12-31 |
NO131420B (no) | 1975-02-17 |
DK128116B (da) | 1974-03-04 |
DE2114887B2 (de) | 1980-01-17 |
SE384368B (sv) | 1976-05-03 |
NO131420C (no) | 1975-05-28 |
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