NO811501L - PROCEDURE FOR THE PREPARATION OF ETHENDIAMINE DERIVATIVES, AND INTERMEDIATES FOR THESE - Google Patents
PROCEDURE FOR THE PREPARATION OF ETHENDIAMINE DERIVATIVES, AND INTERMEDIATES FOR THESEInfo
- Publication number
- NO811501L NO811501L NO811501A NO811501A NO811501L NO 811501 L NO811501 L NO 811501L NO 811501 A NO811501 A NO 811501A NO 811501 A NO811501 A NO 811501A NO 811501 L NO811501 L NO 811501L
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- solution
- dimethylamino
- compounds
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000000543 intermediate Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 44
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 8
- -1 hydroxide ions Chemical class 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- BSGRLBPZSRZQOR-UHFFFAOYSA-N ethene-1,1-diamine Chemical class NC(N)=C BSGRLBPZSRZQOR-UHFFFAOYSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 230000007306 turnover Effects 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 4
- 235000013312 flour Nutrition 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 38
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 238000000921 elemental analysis Methods 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 229960004592 isopropanol Drugs 0.000 description 10
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- OWCCAJROUOTMOE-UHFFFAOYSA-N n-(1-methylsulfanyl-2-nitroethenyl)propan-1-amine Chemical compound CCCNC(SC)=C[N+]([O-])=O OWCCAJROUOTMOE-UHFFFAOYSA-N 0.000 description 4
- NXGHEDHQXXXTTP-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-2-nitroethene Chemical compound CSC(SC)=C[N+]([O-])=O NXGHEDHQXXXTTP-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910001961 silver nitrate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- PEIZXYQRSWRRNQ-UHFFFAOYSA-N 1-[5-(chloromethyl)furan-2-yl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=C(CCl)O1 PEIZXYQRSWRRNQ-UHFFFAOYSA-N 0.000 description 2
- NESLOYMMIUOLMU-UHFFFAOYSA-N 1-n'-methyl-2-nitroethene-1,1-diamine Chemical compound CNC(N)=C[N+]([O-])=O NESLOYMMIUOLMU-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BQRQOLQFLNSWNV-UHFFFAOYSA-N [5-[(dimethylamino)methyl]furan-2-yl]methanol Chemical compound CN(C)CC1=CC=C(CO)O1 BQRQOLQFLNSWNV-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- HUDRYGJMGVJMCD-UHFFFAOYSA-N n,n-dimethyl-1-methylsulfanyl-2-nitroethenamine Chemical group CSC(N(C)C)=C[N+]([O-])=O HUDRYGJMGVJMCD-UHFFFAOYSA-N 0.000 description 2
- YQFHPXZGXNYYLD-UHFFFAOYSA-N n-methyl-1-methylsulfanyl-2-nitroethenamine Chemical compound CNC(SC)=C[N+]([O-])=O YQFHPXZGXNYYLD-UHFFFAOYSA-N 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- YQFHPXZGXNYYLD-ARJAWSKDSA-N (z)-n-methyl-1-methylsulfanyl-2-nitroethenamine Chemical group CN\C(SC)=C\[N+]([O-])=O YQFHPXZGXNYYLD-ARJAWSKDSA-N 0.000 description 1
- VQBVPDAUEBSGMB-UHFFFAOYSA-N 1-n,1-n'-dimethyl-2-nitroethene-1,1-diamine Chemical group CNC(NC)=C[N+]([O-])=O VQBVPDAUEBSGMB-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 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
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- VMXUWOKSQNHOCA-UHFFFAOYSA-N N1'-[2-[[5-[(dimethylamino)methyl]-2-furanyl]methylthio]ethyl]-N1-methyl-2-nitroethene-1,1-diamine Chemical compound [O-][N+](=O)C=C(NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-UHFFFAOYSA-N 0.000 description 1
- BHULOLFDEUJIQK-UHFFFAOYSA-N NC(=C[N+](=O)[O-])NCCC Chemical compound NC(=C[N+](=O)[O-])NCCC BHULOLFDEUJIQK-UHFFFAOYSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- CRHKDRDOMGTZON-UHFFFAOYSA-N [5-(diethylaminomethyl)furan-2-yl]methanol Chemical compound CCN(CC)CC1=CC=C(CO)O1 CRHKDRDOMGTZON-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- MSQDVGOEBXMPRF-UHFFFAOYSA-N cyclohexane;propan-2-one Chemical compound CC(C)=O.C1CCCCC1 MSQDVGOEBXMPRF-UHFFFAOYSA-N 0.000 description 1
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 1
- 229940099500 cystamine Drugs 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 150000008320 nitroethenes Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
- C07D203/12—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Fremgangsmåte ved fremstilling av forbindelser med for-,. mel (I):. 12 3 hvori R, R , R og R er like eller forskjellige og betyr hydrogen eller en lavere alkylgruppe med opptil 3 karbonatomer ved å omsette forbindelsene med form-Ipp (TT1 na lTTT). 3. hvori R, R , R og R har de ovenfor nevnte betydninger .Fremstilling av farmakologisk akseptable salter av forbindelser med formel (I) er også angitt.Process for the preparation of compounds with flour (I) :. Wherein R, R, R and R are the same or different and represent hydrogen or a lower alkyl group having up to 3 carbon atoms by reacting the compounds of form-Ipp (TT1 na 1TTT). Wherein R, R, R and R have the meanings given above. Preparation of pharmacologically acceptable salts of compounds of formula (I) is also indicated.
Description
Foreliggende oppfinnelse vedrører fremgangsmåte ved fremstilling av forbindelser med den generelle formel (I): The present invention relates to a method for the preparation of compounds with the general formula (I):
12 3 12 3
hvori R, R , R og R kan være like eller forskjellige og betyr hydrogen eller en lavere alkylgruppe ikke inneholdende mer enn 3 karbonatomer. wherein R, R , R and R may be the same or different and mean hydrogen or a lower alkyl group containing not more than 3 carbon atoms.
Forbindelse(I) er velkjent å besitte interessante farmasøy-tiske egenskaper. Deres, fremstilling er beskrevet utgående fra N-alkyl-1-(metyltio).-2-nitro-etenaminer og 2-[[[5-(di-alkylamino)-metyl-2-furanyl]-metyl]-tio]-etylaminer (B.J. Price, J.W. Clitherow og J. Bradshau, belgisk patent nr. 857.388. Utbyttene er ikke høyere enn 70% og ytterligere krever denne fremgangsmåte anvendelse av kostbart cystamin som kilde for sekvensen S-C-C-N. I henhold til oppfinnelsen kan forbindelsene (I) fremstilles i høye utbytter og på en meget rimelig måte ved hjelp av omsetning av forbindelsene med de generelle formler (II) og (III).: Compound (I) is well known to possess interesting pharmaceutical properties. Their preparation is described starting from N-alkyl-1-(methylthio).-2-nitro-ethenamines and 2-[[[5-(di-alkylamino)-methyl-2-furanyl]-methyl]-thio]- ethylamines (B.J. Price, J.W. Clitherow and J. Bradshau, Belgian patent no. 857,388. The yields are not higher than 70% and furthermore this method requires the use of expensive cystamine as a source for the sequence S-C-C-N. According to the invention, the compounds (I) can be prepared in high yields and in a very reasonable manner by means of conversion of the compounds of the general formulas (II) and (III).:
12 3 12 3
hvori R, R , R og R har de ovenfor gitte betydninger, i et inert oppløsningsmiddel såsom vann, metanol, etanol; dimetylformamid eller acetonitril i nærvær av baser såsom hydroksyd, metoksyd eller etoksydioner ved temperatur i området -20°C-6 0°C. wherein R, R , R , and R have the meanings given above, in an inert solvent such as water, methanol, ethanol; dimethylformamide or acetonitrile in the presence of bases such as hydroxide, methoxide or ethoxide ions at a temperature in the range -20°C-60°C.
Det er allerede funnet (V. Sunjic et al. Gazz.Chim. Ital. 110 It has already been found (V. Sunjic et al. Gazz.Chim. Ital. 110
(1980) 345-350 og de sveitsiske patentsøknader nr. 16340/77, 5237/78 og 10695/78). at heterocykliske metylentioler gir med etyleniminocyanoazometin den samme sekvens S-C-C-N. Det er nå overraskende funnet at det samme fundamentale reaksjons-skjema også kan anvendes i tilfellet for forbindelsene med formel (III), til tross for tilstedeværelsen av nitroetengrup-j pen med iboende sure egenskaper og med en generell følsomhet (i denne henseende se A. Streitweiser og C.H. Heathcock, Introduction to Organic Chemistry, Colier Mac Millan Int. Edi-tions, New York-London, 1976, side 800-801). Uventet forblir imidlertid denne gruppe stabil også i et basisk medium i det minste i de nevnte temperaturområder og i tilsetningsrekke- . følgen for reaktantene som anvendes ved foreliggende fremgangsmåte. (1980) 345-350 and Swiss Patent Applications Nos. 16340/77, 5237/78 and 10695/78). that heterocyclic methylenethiols give with ethyleneiminocyanoazomethine the same sequence S-C-C-N. It has now surprisingly been found that the same fundamental reaction scheme can also be applied in the case of the compounds of formula (III), despite the presence of the nitroethene group with inherently acidic properties and with a general sensitivity (in this respect see A. Streitweiser and C.H. Heathcock, Introduction to Organic Chemistry, Collier Mac Millan Int. Editions, New York-London, 1976, pages 800-801). Unexpectedly, however, this group remains stable also in a basic medium, at least in the mentioned temperature ranges and in the addition series. consequence for the reactants used in the present method.
Kondensasjonsutbyttene mellom (III og (III) er generelt ca. 80%, hvilket er betydelig høyere enn de beskrevet ved den kjente fremgangsmåte for fremstilling av forbindelsen med formel I. The condensation yields between (III) and (III) are generally about 80%, which is significantly higher than those described in the known method for preparing the compound of formula I.
Foreliggende oppfinnelse vedrører også en fremgangsmåte for fremstilling av nye forbindelser med den generelle formel (III) The present invention also relates to a method for the preparation of new compounds with the general formula (III)
hvori R 2 og R 3 kan være like eller forskjellige og betyr et hydrogenatom, en lavere alkylgruppe inneholdende maksimalt 3 karbonatomer, idet man utgår fra forbindelser med den generelle formel (IV): 2 3 hvori R og R har den ovenfor gitte betydning.som for forbindelsen ifølge formel III og fra etylenimin i nærvær av tiof ile . in which R 2 and R 3 can be the same or different and means a hydrogen atom, a lower alkyl group containing a maximum of 3 carbon atoms, starting from compounds with the general formula (IV): 2 3 in which R and R have the meaning given above. for the compound according to formula III and from ethyleneimine in the presence of thiophile.
metallioner,eksempelvis Cu<+>, Cu^<+>, Zn^ + eller Ag<+>som kataly-satorer i polare oppløsningsmidler såsom acetonitril, metanol eller vann, som på den ene side muliggjør tilstede-værelse av metallioner i oppløsning i tilstrekkelig konsen- i trasjon og på den annen side kvantitativ presipitering av metallmerkaptider ved reaksjonstemperatur vanligvis i området 0-60°C og for gjenvinning av de rene produkter etter kvantitativ separasjon av metallmerkaptidene ved filtrering, met-ning av den vandige oppløsning med ammoniumklorid og behand-ling med ammoniakk inntil pH 10, hvoretter produktene ekstra-heres med diklormetan eller kloroform, inndampning av oppløsningsmiddelet og omkrystallisering av råproduktene fra egnede oppløsnings-midler eller oppløsningsmiddelblandinger. Forbindelsene med formel (III)1, er nye og deres fremstilling er tidligere ikke beskrevet. Oppfinnelsen omfatter således forbindelser med formel (III). metal ions, for example Cu<+>, Cu^<+>, Zn^ + or Ag<+> as catalysts in polar solvents such as acetonitrile, methanol or water, which on the one hand enable the presence of metal ions in solution in sufficient concentration and, on the other hand, quantitative precipitation of metal mercaptides at a reaction temperature usually in the range 0-60°C and for recovery of the pure products after quantitative separation of the metal mercaptides by filtration, saturation of the aqueous solution with ammonium chloride and treatment -ling with ammonia up to pH 10, after which the products are extracted with dichloromethane or chloroform, evaporation of the solvent and recrystallization of the crude products from suitable solvents or solvent mixtures. The compounds with formula (III) 1 are new and their preparation has not previously been described. The invention thus includes compounds of formula (III).
Foreliggende fremgangsmåte byr på den fordel at alkylmerkap-tangruppen i forbindelsene med formel (IV) kan erstattes med etylenimin under milde betingelser og således forhindres en brytning av etyleniminringen, som er kjent for å være ustab-il, i nærvær av visse metallioner som i det etterfølgende er betegnet som "tiofile" såsom Cu .f , Cu<2+>Zn<2+>eller Ag<+>The present method offers the advantage that the alkyl mercaptan group in the compounds of formula (IV) can be replaced by ethyleneimine under mild conditions and thus a breakage of the ethyleneimine ring, which is known to be unstable, is prevented in the presence of certain metal ions as in the are subsequently designated as "thiophiles" such as Cu .f , Cu<2+>Zn<2+>or Ag<+>
Det er velkjent at nukleofile substitueringer i trigonalkar-bonet (sp 2-hybridisering) er energisk ugunstige prosesser It is well known that nucleophilic substitutions in the trigonal carbon (sp 2 hybridization) are energetically unfavorable processes
(se eksempelvis A. Streitweiser og C.H. Heatchcock, Introduction to Organic Chemistry, Collier Macmillan Int. Ed., 1976, New York and London, side 893-898 og J.B. Hendrickson, (see for example A. Streitweiser and C.H. Heatchcock, Introduction to Organic Chemistry, Collier Macmillan Int. Ed., 1976, New York and London, pages 893-898 and J.B. Hendrickson,
t h t h
D.J. Cram, G.S. Hammond, Organic Chemistry, 3 ed., 1970, McGraw-Hill, side 445). DJ Cram, G.S. Hammond, Organic Chemistry, 3 ed., 1970, McGraw-Hill, page 445).
Overraskende vil den aktiverende effekt av metallionene på karbon-svovelbindingen i forbindelser med den generelle formel (IV) muliggjøre nukleofil substituering med etylenimin til det etyleniske karbonatcm under meget milde betingelser. Surprisingly, the activating effect of the metal ions on the carbon-sulfur bond in compounds of the general formula (IV) will enable nucleophilic substitution with ethyleneimine of the ethylenic carbonate cm under very mild conditions.
Foreliggende oppfinnelse vedrører også en fremgangsmåte ved fremstilling av nye furanderivater med den generelle formel i The present invention also relates to a method for the production of new furan derivatives with the general formula i
eller deres stabile salter hvor R og R^betyr et hydrogenatom eller en lavere alkylgruppe, fortrinnsvis med 1-3 kar- ' bonatomer, idet det utgås fra en forbindelse med den generelle formel (V) hvori R og R^har den samme betydning som i formel II, mens X representerer klor eller brom eller en tioureidgruppe (-SC (=NH)). • Hvis X betyr klor eller brom vil foreliggende fremgangsmåte muliggjøre en omsetning av de respektive forbindelser (V) med natrium- eller kaliumhydrosulfid i protiske oppløsningsmidler såsom lavere alkoholer eller vann. På den annen side hvis X er en tioureidgruppe utføres en hydrolyse med kaliumhydroksyd i metanol eller vann ved temperaturer fortrinnsvis i området fra romtemperatur til tilbakeløps-temperaturen for blandingen. Forbindelsene med den generelle formel (II) blir deretter isolert i form av deres stabile salter såsom hydroklorider eller hydrobromider. De to ovenfor nevnte alternativer kan skjematisk fremstilles som føl-ger : or their stable salts where R and R^ mean a hydrogen atom or a lower alkyl group, preferably with 1-3 carbon atoms, starting from a compound of the general formula (V) in which R and R^ have the same meaning as in formula II, while X represents chlorine or bromine or a thioureide group (-SC (=NH)). • If X means chlorine or bromine, the present method will enable a reaction of the respective compounds (V) with sodium or potassium hydrosulphide in protic solvents such as lower alcohols or water. On the other hand, if X is a thioureide group, a hydrolysis with potassium hydroxide in methanol or water is carried out at temperatures preferably in the range from room temperature to the reflux temperature of the mixture. The compounds of the general formula (II) are then isolated in the form of their stable salts such as hydrochlorides or hydrobromides. The two above-mentioned alternatives can be schematically presented as follows:
De ovenfor nevnte forbindelser er nyttige som mellomprodukter ved fremstilling av forbindelser som er effektive ved mave-sårterapi (se eksempelvis H.G. Dammon et al., Deutsche Med. Wochenschr. 104, 1676 (1979)). Selv om litteraturen under fremstilling av 5- (N,N-dimetylamino).metyl-2-hydroksymetylfuran ved hjelp av dimetylaminometylering ifølge Mannich av 2-hydroksymetylfuran (se eksempelvis A.P. Dunlop og F.N. Peters, The Furanes, 1953, Reinhold Publ. Corp., New York, side 222, W. Holdren, J. Amer. Chem. Soc. 69; 464 (1947)), har.de lave utbytter (11-45%). utelukket en økonomisk fordel av denne forbindelse som et utgangsmateriale. I et nylig utstedet patent (U.S. Patent nr. 4.128.657) er vist fremstilling av visse 2-hydroksymetylfuraner i vandig oppløsning med utbytter høyere enn 50%. i henhold til The above-mentioned compounds are useful as intermediates in the preparation of compounds effective in gastric ulcer therapy (see, for example, H.G. Dammon et al., Deutsche Med. Wochenschr. 104, 1676 (1979)). Although the literature on the preparation of 5-(N,N-dimethylamino).methyl-2-hydroxymethylfuran by means of dimethylaminomethylation according to Mannich of 2-hydroxymethylfuran (see for example A.P. Dunlop and F.N. Peters, The Furanes, 1953, Reinhold Publ. Corp. , New York, page 222, W. Holdren, J. Amer. Chem. Soc. 69; 464 (1947)), have low yields (11-45%). ruled out an economic benefit of this compound as a starting material. In a recently issued patent (U.S. Patent No. 4,128,657) the preparation of certain 2-hydroxymethylfurans in aqueous solution with yields higher than 50% is shown. according to
et annet trekk ved foreliggende oppfinnelse under anvendelse av paraformaldehyd i metanoloppløsning ved høy temperatur er utbyttet av 5-(N,N-dialkylamino).-metyl-2-hydroksymetyl-fura-ner (V, hvor X = OH.) høyere enn 90%. another feature of the present invention using paraformaldehyde in methanol solution at high temperature is the yield of 5-(N,N-dialkylamino).-methyl-2-hydroxymethyl-furans (V, where X = OH.) higher than 90 %.
Som tidligere nevnt er forbindelsene ifølge den generelle formel (i)effektive ved mavesårkjemoterapi, spesielt forbind-12 3 eisene hvori R, R og R betyr en metylgruppe mens R er hydrogen (W. Domschke et. al. Lancet 1979, 320).. As previously mentioned, the compounds according to the general formula (i) are effective in peptic ulcer chemotherapy, especially the compounds in which R, R and R mean a methyl group while R is hydrogen (W. Domschke et. al. Lancet 1979, 320).
De følgende eksempler illustrerer oppfinnelsen.The following examples illustrate the invention.
Eksempel 1Example 1
1- metylamino- l- metyltio- 2- nitroeten 1- methylamino- 1- methylthio- 2- nitroethene
1,l-bis-metyltio-2-nitroeten (16,4 g, 0,10 mol) ble oppløst i varm toluen (200 ml) og en etanolisk oppløsning av metylamin (25 ml 30%-ig oppløsning, 0,25- mol metylamin) fortynnet med 40 ml toluen og tilsatt i løpet av 30 min. ved tilbake-løpstemperatur. Etter en time under tilbakeløp og omrøring ble de presipiterte krystaller separert fra den varme opp-løsning ved hjelp av filtrering. På denne måte blé ca. 1 g i av et halvrent produkt erholdt, nemlig 1,1-bis-metylamino-2-nitroeten, smp. 214-215°C (fra 2-propanol). IR(KBr).: 3180-3300 (bredt bånd)., 1625-1580, 14 28,13 60-1380 (bredt bånd), 1230 (bredt bånd), 995, 752, 645 cm"<1>. NMR (CDClg).: 2,88 (d, 6H, sammenfaller i s ved tilsetning av D^ O)., 6,55 (s, 1H).. The 1,1-bis-methylthio-2-nitroethene (16.4 g, 0.10 mol) was dissolved in hot toluene (200 mL) and an ethanolic solution of methylamine (25 mL 30% solution, 0.25- mol methylamine) diluted with 40 ml toluene and added over 30 min. at return temperature. After one hour under reflux and stirring, the precipitated crystals were separated from the hot solution by means of filtration. In this way approx. 1 g of a semi-pure product obtained, namely 1,1-bis-methylamino-2-nitroethylene, m.p. 214-215°C (from 2-propanol). IR(KBr).: 3180-3300 (broad band)., 1625-1580, 14 28.13 60-1380 (broad band), 1230 (broad band), 995, 752, 645 cm"<1>. NMR ( CDClg).: 2.88 (d, 6H, coincides in s on addition of D^O)., 6.55 (s, 1H)..
Elementæranalyse: f or C4HgN302(131,14).Elemental analysis: for C4HgN3O2(131.14).
Beregnet %: C 36,65; H 6,91; N 32,05Calculated %: C 36.65; H 6.91; N 32.05
Funnet: C 36,68; H 6,84; N 31,80. Found: C 36.68; H 6.84; NOK 31.80.
Den filtrerte væske blir inndampet til et volum på ca. 150 ml og deretter avkjølt i is over natten. De utfelte krystaller ble separert ved hjelp av filtrering og tørket til å gi 11,8 g (80%) utbytte av det rene l-metylamino-l-metyltio-2-nitroeten, smp. 105-106°C. Ved omkrystallisering fra etylacetat, smp. 109-110°C. The filtered liquid is evaporated to a volume of approx. 150 ml and then cooled in ice overnight. The precipitated crystals were separated by filtration and dried to give 11.8 g (80%) yield of the pure 1-methylamino-1-methylthio-2-nitroethylene, m.p. 105-106°C. On recrystallization from ethyl acetate, m.p. 109-110°C.
IR (KBr): 3200,1620, 1465, 1395, 1340, 1230-1250 (bredt bånd), 995, 820, 760, 660 cm"<1.>IR (KBr): 3200,1620, 1465, 1395, 1340, 1230-1250 (broad band), 995, 820, 760, 660 cm"<1.>
NMR(CDC13).: 2,51 (s, 3H) , 3,20 (d, 3H, sammenfaller i s ved tilsetning av D20) , 6,68 (s, 1H).. NMR(CDC13).: 2.51 (s, 3H) , 3.20 (d, 3H, coincides in s on addition of D2O) , 6.68 (s, 1H)..
Elementæranalyse: for C4HgN2S02(148,18)Elemental analysis: for C4HgN2S02(148.18)
Beregnet %: C 32,41; H 5,44; N 18,98Calculated %: C 32.41; H 5.44; N 18.98
Funnet: C 32,41; H 5,51; N 19,28. Found: C 32.41; H 5.51; N 19,28.
Eksempel 2Example 2
1- n- propylamino- 1- metyltio- 2- nitroeten1- n- propylamino- 1- methylthio- 2- nitroethene
Under anvendelse av de samme betingelser som i eksempel 1 og utgående fra 1,64 g (10,0 mmol) av 1,l-dimetyltio-2-nitroeten og 3,0 ml av en 50%-ig etanolisk oppløsning av n-propylamin ble omset ningen utført i 70 min. Oppløsningsmiddelet ble inndampet til tørrhet og residuet omkrystallisert fra etylacetat (ca. 10 ml), og det ble erholdt ca. 200 mg bis-1,1-n-propylamino-: 2-nitroeten, smp. 120-121°C. IR(KBr): 3250, 2840-2880 (tre bånd), 1620, 1575 (bredt bånd), 1380-1410 (bredt bånd), 1220 (bredt bånd), 1010, 755 cm<-1>. NMR(CDC13): 1,0 (t, 6H) , 1,2-2,0 (m, 4H) , 3,0-3,6 (m, 4H) , 6,72 (s, iH). Using the same conditions as in Example 1 and starting from 1.64 g (10.0 mmol) of 1,1-dimethylthio-2-nitroethylene and 3.0 ml of a 50% ethanolic solution of n-propylamine the transaction was carried out in 70 min. The solvent was evaporated to dryness and the residue recrystallized from ethyl acetate (ca. 10 ml), and there was obtained ca. 200 mg of bis-1,1-n-propylamino-:2-nitroethylene, m.p. 120-121°C. IR(KBr): 3250, 2840-2880 (three bands), 1620, 1575 (broad band), 1380-1410 (broad band), 1220 (broad band), 1010, 755 cm<-1>. NMR (CDCl 3 ): 1.0 (t, 6H), 1.2-2.0 (m, 4H), 3.0-3.6 (m, 4H), 6.72 (s, 1H).
i' Elementæranalyse for:<C>8Hi7N3°2(187,24). i' Elemental analysis for:<C>8Hi7N3°2(187.24).
Beregnet %: C 51,31; H 9,15; N 22,44Calculated %: C 51.31; H 9.15; N 22.44
Funnet: C 51,31; H 9,25; N 22,34. Found: C 51.31; H 9.25; N 22,34.
Den filtrerte oppløsning ble inndampet og den gjenværende olje omkrystallisert fra n-heptan til å gi 1,12 g (63,6%) rent 1-n-propylamino-l-metyltio-2-nitroeten, smp. 64-65° C. IR(KBr): 3140, 2840-3000 (fire bånd), 1560, 1455, 1420, 1330, 1305, 1210, 970, 825, 765, 680 cm"<1.>The filtered solution was evaporated and the remaining oil recrystallized from n-heptane to give 1.12 g (63.6%) of pure 1-n-propylamino-1-methylthio-2-nitroethylene, m.p. 64-65° C. IR(KBr): 3140, 2840-3000 (four bands), 1560, 1455, 1420, 1330, 1305, 1210, 970, 825, 765, 680 cm"<1.>
NMR(CDC13); 1,05 (t, 3H), 1,3-2,0 (m, 2H), 2,50 (s, 3H), NMR (CDCl 3 ); 1.05 (t, 3H), 1.3-2.0 (m, 2H), 2.50 (s, 3H),
3,48 (q, 2H) , 6,70 (s, 1H).. 3.48 (q, 2H), 6.70 (s, 1H)..
Elementæranalyse for:<C>gH^^C^S (176, 24)Elemental analysis for:<C>gH^^C^S (176, 24)
Beregnet %: C 40,88; H 6,86; N 15,89Calculated %: C 40.88; H 6.86; N 15.89
Funnet: C 40,91; H 6,98; N 15,91. Found: C 40.91; H 6.98; N 15.91.
Eksempel 3Example 3
l- dimetylamino- l- metyltio- 2- nitroeten l-Dimethylamino-l-methylthio-2-nitroethene
1,l-dimetyltio-2-nitroeten (3,30 g, 20,0 mmol) ble oppløst 1 diklormetan (150 ml) og dimetylaminhydroklorid (4,08 g, The 1,1-dimethylthio-2-nitroethene (3.30 g, 20.0 mmol) was dissolved in 1 dichloromethane (150 mL) and dimethylamine hydrochloride (4.08 g,
50,0 mmol) og natriummetoksyd (2,67 g, 50,0 mmol) ble tilsatt. Reaksjonsblandihgen ble oppvarmet og holdt ved til-bakeløpstemperaturen i 1 h,og deretter avkjølt og eddiksyre 2 M (50 ml) ble tilsatt. Den organiske fase ble separert 50.0 mmol) and sodium methoxide (2.67 g, 50.0 mmol) were added. The reaction mixture was heated and held at the reflux temperature for 1 h, then cooled and acetic acid 2 M (50 ml) was added. The organic phase was separated
og vannfasen ekstrahert med diklorometan (3x60 ml). Det organiske ekstrakt ble tørket over (Nå2SOjj). , inndampet og den gjenværende olje renset på en silikagelkolonne under anvendelse av etylacetat som elueringsmiddel. and the aqueous phase extracted with dichloromethane (3x60 ml). The organic extract was dried over (N 2 SO 4 ). , evaporated and the remaining oil purified on a silica gel column using ethyl acetate as eluent.
Den første fraksjonen inneholdt ca. 5% av utgangsforbind- eisen, deretter fulgte 2,20 g (68%) av det rene 1-dimetylamino-l-metyltio-2-nitroeten, smp. 60-61 o C.<.1>'IR(KBr): 2900-3040 (tre bånd), 1572, 1450, 1410, 1395, 1335, 1205, 942, 680 cm"<1>ble oppnådd. i NMR(CDC13): 2,52 (s, 3H) , 3,31 (s., 6H) , 6,66 (s, 1H).. The first fraction contained approx. 5% of the starting compound, then followed 2.20 g (68%) of the pure 1-dimethylamino-1-methylthio-2-nitroethylene, m.p. 60-61 o C.<.1>'IR(KBr): 2900-3040 (three bands), 1572, 1450, 1410, 1395, 1335, 1205, 942, 680 cm"<1>was obtained. in NMR( CDCl 3 ): 2.52 (s, 3H) , 3.31 (s., 6H) , 6.66 (s, 1H)..
Elementæranalyse for:<C>5<H>1QN2<0>2<S>(162,21)Elemental analysis for:<C>5<H>1QN2<0>2<S>(162,21)
Beregnet I: C 37,01; H 6,21; N 17,27 Funnet: C 36,88; H 6,17; N 17,44. Calculated I: C 37.01; H 6.21; N 17.27 Found: C 36.88; H 6.17; N 17.44.
Eksempel 4Example 4
l- etylenimino- l- metylamino- 2- nitroeten l- ethyleneimino- l- methylamino- 2- nitroethene
i-metylamino-l-metyltio-2-nitroeten (37,0 g, 0,25 mol) ble tilsatt i små porsjoner til en oppløsning av etylenimin (150 ml), sølvnitrat (42,5 g) , og 2M NaOH (125 ml), i vann (1,5 1). i-Methylamino-1-methylthio-2-nitroethene (37.0 g, 0.25 mol) was added in small portions to a solution of ethyleneimine (150 mL), silver nitrate (42.5 g), and 2M NaOH (125 ml), in water (1.5 1).
Etter 2 h omrøring ved romtemperatur ble det dannede sølvmer-kaptid frafiltrert og vasket méd vann. Filtratet ble mettet med ammoniumklorid og tilsatt konsentrert ammoniakk til pH 10 og ektrahert med diklormetan (3 x 500 ml) og de organiske ekstrakter tørket over (Na-jSO^). og restoljen krystallisert fra etylacetat til å gi 30,7 g (86%) rent 1-etylenimino-l-metylamino-2-nitroeten, smp. 133-134°C. IR(KBr).: 3220, 1615, 1508, 1405, 1380, 1290, 1240, 1155, 1110, 825, 755, 660 cm"<1.>NMR(DMSO-d,): 2,40 (s, 4H), 3,10 (d, 3H, sammenfaller i s ved tilsetning av D20), 6,62 (s, 1H) ble erholdt. After stirring for 2 h at room temperature, the silver mercaptide formed was filtered off and washed with water. The filtrate was saturated with ammonium chloride and added concentrated ammonia to pH 10 and extracted with dichloromethane (3 x 500 ml) and the organic extracts dried over (Na-2SO4). and the residual oil crystallized from ethyl acetate to give 30.7 g (86%) of pure 1-ethyleneimino-1-methylamino-2-nitroethylene, m.p. 133-134°C. IR(KBr): 3220, 1615, 1508, 1405, 1380, 1290, 1240, 1155, 1110, 825, 755, 660 cm"<1>NMR(DMSO-d,): 2.40 (s, 4H ), 3.10 (d, 3H, coincides in s upon addition of D 2 O), 6.62 (s, 1H) was obtained.
Elementæranalyse for: C^HgN^O,, (143,15)..Elemental analysis for: C^HgN^O,, (143.15)..
Beregnet I: C 41,95; H 6,34; N 29,35Calculated I: C 41.95; H 6.34; N 29.35
Funnet: C 41,93; H 6,47; N 29,68. Found: C 41.93; H 6.47; N 29.68.
Eksempel 5Example 5
l- etylenimino- l- metylamino- 2- nitroetenl- ethyleneimino- l- methylamino- 2- nitroethene
Ved å utgå fra 7,4 g (0,05 mol) l-metylamino-l-metyltio-2-nitroeten, 3,0 ml etylenimin, 25-ml av en 2M natriumhydroksyd-oppløsning og 4,0 g kobber (I) klorid ble reaksjonen utført i acetonitril (180 ml) ved 40-50°C i 3 h. Etter filtrering av kobbermerkaptidet ble oppløsningsmiddelet avdéstillert ved 30-40°C under vakuum og råproduktet omkrystallisert fra 1 etylacetat til å gi 7,1 g av den rene tittelforbindelse, smp. smp. 132-134°C. Starting from 7.4 g (0.05 mol) of 1-methylamino-1-methylthio-2-nitroethene, 3.0 ml of ethyleneimine, 25 ml of a 2M sodium hydroxide solution and 4.0 g of copper (I) chloride, the reaction was carried out in acetonitrile (180 ml) at 40-50°C for 3 h. After filtering the copper mercaptide, the solvent was distilled off at 30-40°C under vacuum and the crude product recrystallized from 1 ethyl acetate to give 7.1 g of the pure title compound, m.p. m.p. 132-134°C.
Eksempel 6 1- etylenimino- 1- n- propylamino- 2- nitroeten Example 6 1-ethyleneimino-1-n-propylamino-2-nitroethene
3,50 g (20,0 mmol) l-n-propylamino-l-metyltio-2-nitroeten i 150 ml 1%-ig etylen iminoppløsning i vann, til hvilken var tilsatt sølvnitrat (4,25 g). og natriumhydroksydet 2M (12,5 ml) 3.50 g (20.0 mmol) of 1-n-propylamino-1-methylthio-2-nitroethylene in 150 ml of 1% ethylene imine solution in water, to which was added silver nitrate (4.25 g). and the sodium hydroxide 2M (12.5 ml)
i ble omsatt i 30 min. ved romtemperatur. Sølvmerkapti.der ble; deretter filtrert fra og vasket med vann og filtratet mettet 1 med NH^Cl og tilsatt konsentrert ammoniakk til pH 10. Blandingen ble ekstrahert med CH2C12(3 x 10 ml) og de organiske ekstrahert over (Na^SO^). og inndampet til tørrhet. Restoljen ble omkrystallisert fra 2-propanol til å gi 2,21 g (64,9%). rent l-etylenimino-l-n-propylamino-2-nitroeten, smp. 77-78°C. IR(KBr): 3130, 2850-2970 (fire bånd), 1595, 1505, 1410, 1290, 1220, 1160 (to bånd), 1060, 1112, 830 cm"<1>. i was traded for 30 min. at room temperature. Sølvmerkapti.der became; then filtered off and washed with water and the filtrate saturated 1 with NH^Cl and added concentrated ammonia to pH 10. The mixture was extracted with CH 2 Cl 2 (3 x 10 ml) and the organics extracted over (Na^SO^). and evaporated to dryness. The residual oil was recrystallized from 2-propanol to give 2.21 g (64.9%). pure l-ethyleneimino-l-n-propylamino-2-nitroethylene, m.p. 77-78°C. IR(KBr): 3130, 2850-2970 (four bands), 1595, 1505, 1410, 1290, 1220, 1160 (two bands), 1060, 1112, 830 cm"<1>.
NMR (DMSO-dg): 2,40 (s, 4H)., 3,10 (d, 3H, sammenfaller i s ved tilsetning av D20), 6,62 (s, 1H). NMR (DMSO-dg): 2.40 (s, 4H)., 3.10 (d, 3H, coincides in s on addition of D 2 O), 6.62 (s, 1H).
Elementæranalsyse for:<C>7Hi3N3°2(171,19).Elemental analysis for:<C>7Hi3N3°2(171.19).
Beregnet %: C 49,10; H 7,05;. N 24,54Calculated %: C 49.10; H 7.05;. N 24.54
Funnet: C 49,37; H 7,44; N 24,49. Found: C 49.37; H 7.44; N 24.49.
Eksempel 7Example 7
1- etylenimino- 1- n- propylamino- 2- nitroeten l-n-propylamino-l-metyltio-2-nitroeten (7,0 g, 40,0 mmol) ble oppløst i acetonitril og satt til en vandig etyleniminoppløs-ning (30 ml 10%-ig H20-oppløsning). Sink (II) klorid (3,80 g) og natriumhydroksyd ble deretter tilsatt og den erholdte opp-løsning omrørt ved 35°C i 8 h. Utfélt sinkmerkaptid ble vakuumfiltrert og den filtrerte oppløsning behandlet som beskrevet i eksempel 6 til å gi 6,22 g av den rene tittelfor- . bindelse, smp. 77-78°C... 1-ethyleneimino-1-n-propylamino-2-nitroethene 1-n-propylamino-1-methylthio-2-nitroethene (7.0 g, 40.0 mmol) was dissolved in acetonitrile and added to an aqueous ethyleneimine solution (30 ml 10% H20 solution). Zinc (II) chloride (3.80 g) and sodium hydroxide were then added and the resulting solution stirred at 35°C for 8 h. Precipitated zinc mercaptide was vacuum filtered and the filtered solution treated as described in Example 6 to give 6, 22 g of the pure title compound. bond, m.p. 77-78°C...
Eksempel 8Example 8
l- etylenimino- l- dimetylamino- 2- nitroeten l- ethyleneimino- l- dimethylamino- 2- nitroethene
1-dimetylamino-l-metyltio-2-nitroeten (8,1 g, 50 mmol) ble oppløst i en 10%-ig vandig etyleniminoppløsning (40 ml) og 1-Dimethylamino-1-methylthio-2-nitroethene (8.1 g, 50 mmol) was dissolved in a 10% aqueous ethyleneimine solution (40 mL) and
satt til en vandig oppløsning inneholdende sølvnitrat (8,5 g, 50 mmol) og natriumhydroksyd (25 ml 2M vandig oppløsning). added to an aqueous solution containing silver nitrate (8.5 g, 50 mmol) and sodium hydroxide (25 mL of 2M aqueous solution).
Etter 4 h omrøring ved 0°C ble sølvmerkaptidet yakuumfiltrert og filtratet behandlet som beskrévet i eksempel 5. Råproduk-; tet (9,4 g) ble omkrystallisert fra etylacetat til å gi 8,1 g ! av det rene tittelprodukt, smp. 82-84°C. IR(KBr\: 1610, 1515, 1400, 1392, 1228, 1170-1790 (bredt bånd), 820, 665 cm"<1>. After stirring for 4 h at 0°C, the silver mercaptide was vacuum filtered and the filtrate treated as described in example 5. Raw product-; tet (9.4 g) was recrystallized from ethyl acetate to give 8.1 g ! of the pure title product, m.p. 82-84°C. IR(KBr\: 1610, 1515, 1400, 1392, 1228, 1170-1790 (broad band), 820, 665 cm"<1>).
NMR (DMSO-d,): 2,42 (s, 4H) , 3,14 (s, 6H) , 6,60 (s, 1H) . .' Elementæranalyse for: C5HnN3°2(157,15) j ; Beregnet %: C 51,07; H 7,86; N 29,78 NMR (DMSO-d 1 ): 2.42 (s, 4H), 3.14 (s, 6H), 6.60 (s, 1H). .' Elemental analysis for: C5HnN3°2(157.15) j ; Calculated %: C 51.07; H 7.86; N 29.78
Funnet: C 50,90; H 7,73; M 29,49. Found: C 50.90; H 7.73; M 29.49.
Eksempel 9Example 9
5-( N, N- dimetylamino) metyl- 2- hydroksymetyl- furan 2-hydroksymety1-furan (49,0 g, 0,50 mol) ble satt til en suspensjon av 21 g (6,70 mol) paraformaldehyd i en oppløsning (ca. 25%) dimetylaminhydroklorid i metanol (44,8 g, 0,55 mol i 200 ml metanol). Den resulterende blanding blé omrørt i 0,5 h ved romtemperatur og deretter oppvarmet til tilbake-løpstemperaturen i 12 h. Metanolen ble aydestillert under vakuum og restoljen behandlet med 0,5 1 5%-ig natriumhydrokr-sydoppløsning mettet med natriumklorid (90-100 g), og ekstrahert med etylacetat (400 + 2 x 200 ml). De organiske ekstrakter ble oppsamlet, tørket over natriumsulfat og inndampet. Det ble erholdt 77 g (99,4 %) av råproduktet i form av en rød olje, som kan anvendes uten ytterligere rensing i de etter-følgende fremstillinger. 5-(N,N-dimethylamino)methyl-2-hydroxymethyl-furan 2-hydroxymethyl-furan (49.0 g, 0.50 mol) was added to a suspension of 21 g (6.70 mol) of paraformaldehyde in a solution (ca. 25%) dimethylamine hydrochloride in methanol (44.8 g, 0.55 mol in 200 ml methanol). The resulting mixture was stirred for 0.5 h at room temperature and then heated to the reflux temperature for 12 h. The methanol was distilled off under vacuum and the residual oil treated with 0.5 1 5% sodium hydroxide solution saturated with sodium chloride (90-100 g), and extracted with ethyl acetate (400 + 2 x 200 ml). The organic extracts were collected, dried over sodium sulfate and evaporated. 77 g (99.4%) of the crude product were obtained in the form of a red oil, which can be used without further purification in the subsequent preparations.
Det rene produkt (72,9 g, 94,2%). ble erholdt ved destillasjon (100-110°C/0,5-0,7 mmHg). NMR (MeOH-d4): 2,29 (s, 6H), 3,54 (s, 2H), 4,55 (s, 2H), 6,30 (s, 2H). The pure product (72.9 g, 94.2%). was obtained by distillation (100-110°C/0.5-0.7 mmHg). NMR (MeOH-d 4 ): 2.29 (s, 6H), 3.54 (s, 2H), 4.55 (s, 2H), 6.30 (s, 2H).
Eksempel 10Example 10
5-( N, N- dietylamino) metyl- 2- hydroksymetyl- furan5-(N,N-diethylamino)methyl-2-hydroxymethyl- furan
Ved å utgå fra 2-hydroksymetylfuran (24,5 g, 0,25 mol), for-maldehyd (125 g), og dietylaminhydroklorid (32,8 g, 0,30 mol) ble reaksjonen utført i metanol (120 ml)_ under anvendelse av betingelsene i henhold til eksempel 9. j Det ble erholdt 42 g (92 %). av det rene produkt, kp.: 140- 144°C/0,6-0, 9 mmHg.^, Starting from 2-hydroxymethylfuran (24.5 g, 0.25 mol), formaldehyde (125 g), and diethylamine hydrochloride (32.8 g, 0.30 mol), the reaction was carried out in methanol (120 ml)_ using the conditions according to Example 9. 42 g (92%) were obtained. of the pure product, bp.: 140-144°C/0.6-0.9 mmHg.^,
i Elementæranalyse for: C^qH-^NO., (183,25) in Elementary analysis for: C^qH-^NO., (183.25)
Beregnet %: C 65,57; H 9,33; N 7,64 I Funnet: C 65,41; H 9,09; N 7,59. Calculated %: C 65.57; H 9.33; N 7.64 I Found: C 65.41; H 9.09; N 7.59.
Eksempel 11 5- ( N, N- dimetylamino) - metyl- 2- brommetyl- f uranhydrobromid. Til en oppløsning av 5- (N,N-dimetylamino).métyl-2-hydroksy>-v Example 11 5-(N,N-dimethylamino)-methyl-2-bromomethyl-furan hydrobromide. To a solution of 5-(N,N-dimethylamino).methyl-2-hydroxy>-v
i. metylfuran (6,20 g, 0,04 mol) i CHC13(100 ml)., ble langsomt tilsatt en 40%-ig hydrobromsyreoppløsning i eddiksyre (5 ml) ved romtemperatur under omrøring. Det organiske oppløsnings-middel ble deretter avdestillert og det erholdte faststoff oppløst i 2-propanol (60 ml), filtrert med trekull (0,5 g) og avkjølt til 0°C og tittelforbindelsen ble erholdt med et utbytte på 87% (10,5 g), smp. 176-177°C (fra acetonitril).. in. methylfuran (6.20 g, 0.04 mol) in CHCl 3 (100 ml)., was slowly added a 40% hydrobromic acid solution in acetic acid (5 ml) at room temperature with stirring. The organic solvent was then distilled off and the resulting solid dissolved in 2-propanol (60 ml), filtered with charcoal (0.5 g) and cooled to 0°C and the title compound was obtained in a yield of 87% (10, 5 g), m.p. 176-177°C (from acetonitrile)..
IR (KBr): 3000-2500, 3110, 1540, 1470, 1415, 1250, 1240, 1230, 1205, 1030, 1010, 975, 820, 760, 660 cm"<1.>: NMR (MeOH-d4): 2,95 (s, 6H), 4,50 (s, 2H), 4,70 (s, -2H1, 6,65 (d, 1H, J=3,5 Hz), 6,87 (d, 1H, J=3,5 Hz). IR (KBr): 3000-2500, 3110, 1540, 1470, 1415, 1250, 1240, 1230, 1205, 1030, 1010, 975, 820, 760, 660 cm"<1.>: NMR (MeOH-d4): 2.95 (s, 6H), 4.50 (s, 2H), 4.70 (s, -2H1, 6.65 (d, 1H, J=3.5 Hz), 6.87 (d, 1H , J=3.5 Hz).
Elementæranalyse for: CgH13NOBr2 . (299,02)Elemental analysis for: CgH13NOBr2 . (299.02)
Beregnet %: C 32,13; H 4,38; N 4,68Calculated %: C 32.13; H 4.38; N 4.68
Funnet: C 32,06; H 4,48; N 4,66. Found: C 32.06; H 4.48; N 4.66.
Eksempel 12 Example 12
5-( N, N- dimetylamino) metyl- 2- klormetylfuranhydroklorid Til en oppløsning av 5-(N,N-dimetylamino)metyl-2-hydroksymetylfuran (6,20 g, 0,04 mol) i CHC13(100 ml) ble tilsatt dråpevis i løpet av 30 min. ved romtemperatur en oppløsning av S0C12(4,8 g, 0,042 mol) i CHCl3(30 ml). Det organiske oppløsningsmiddel ble deretter inndampet og den faste rest oppløst i kokende 2-propanol (50 ml). Fra den ovenfor nevnte oppløsning, avkjølt til 0°C utkrystalliserte tittelforbindelsen med et utbytte på 90% (7,5 g).,. smp. 174-175°C (fra eta-hol) .. 5-(N,N-dimethylamino)methyl-2-chloromethylfuran hydrochloride To a solution of 5-(N,N-dimethylamino)methyl-2-hydroxymethylfuran (6.20 g, 0.04 mol) in CHCl 3 (100 ml) was added added drop by drop over 30 min. at room temperature a solution of SOCl 2 (4.8 g, 0.042 mol) in CHCl 3 (30 mL). The organic solvent was then evaporated and the solid residue dissolved in boiling 2-propanol (50 ml). From the above solution, cooled to 0°C, the title compound crystallized in a yield of 90% (7.5 g). m.p. 174-175°C (from eta-hol) ..
IR(KBr): 3200-2500, 1550, 1480, 1420, 1260, 1230, 1205, 1020, 1050, 980, 820, 755 cm"1. NMR (MeOH-d4): 2,95 (s, 6H), 4,70: (s, 2H), 4,62 (s, 2H), 6,65 (d, 1H, J=3,5 Hz), 6,87 (d, 2H, IR(KBr): 3200-2500, 1550, 1480, 1420, 1260, 1230, 1205, 1020, 1050, 980, 820, 755 cm"1. NMR (MeOH-d4): 2.95 (s, 6H), 4.70: (s, 2H), 4.62 (s, 2H), 6.65 (d, 1H, J=3.5 Hz), 6.87 (d, 2H,
J=3,5 Hz)..J=3.5 Hz)..
Elementæranalyse for: CQH13N0C12(210,10) Beregnet %: C 45,73; H 6,23; N 6,66 Funnet: C 45,61; H 6,19; N 6,51. i Elemental analysis for: CQH13N0C12(210.10) Calculated %: C 45.73; H 6.23; N 6.66 Found: C 45.61; H 6.19; N 6.51. in
Eksempel 13 Example 13
5- ( N, N- dimetylamino) metyl- 2- S- isotioureylitietylfurandihyd. ro-klorid ■ ; 5-(N,N-Dimethylamino)methyl-2-S-isothioureyllithiethylfurandihyde. ro chloride ■ ;
i Til en oppløsning av tiourea (38,06 g, 0,50 mol) i 650 ml 22%-ig saltsyre i 2-propanol ble tilsatt 5-(dimetylamino) metyl-2-hydroksymetylfuran . (77 , 5 g; 0,50 mol).. i To a solution of thiourea (38.06 g, 0.50 mol) in 650 ml of 22% hydrochloric acid in 2-propanol was added 5-(dimethylamino)methyl-2-hydroxymethylfuran. (77 , 5 g; 0.50 mol)..
Den resulterende oppløsning ble oppvarmet til tilbakeløps-temperaturen i 10 h. Ved avkjøling og under sterk omrøring utkrystalliserte reaksjonsproduktet seg i form av små pris-matiske krystaller. Det filtrerte råprodukt ble vasket med 3x3 0 ml 2-propanol. Etter vakuumtørking ble det erholdt 138 g (96,5%) av tittelforbindelsen med et smeltepunkt på 172-174°C. Ved omkrystållisering fra absolutt etanol ble den rene tittelforbindelse erholdt, smp. 174-175°C. IR(KB).: 3020, 1668, 1440, 1255, 1115, 1002, 975, 935, 820, 690 The resulting solution was heated to the reflux temperature for 10 h. On cooling and with vigorous stirring, the reaction product crystallized out in the form of small prismatic crystals. The filtered crude product was washed with 3 x 30 ml of 2-propanol. After vacuum drying, 138 g (96.5%) of the title compound with a melting point of 172-174°C were obtained. By recrystallization from absolute ethanol, the pure title compound was obtained, m.p. 174-175°C. IR(KB).: 3020, 1668, 1440, 1255, 1115, 1002, 975, 935, 820, 690
-1 -1
cm cm
NMR (D20) : 2,96 : (s, 6H). , 4,50 (s, 2H). , 4,62 (s, 2H)., 6,68 dd, 2H, J=4Hz);. NMR (D 2 O) : 2.96 : (s, 6H). , 4.50 (p, 2H). , 4.62 (s, 2H)., 6.68 dd, 2H, J=4Hz);.
Elementæranalyse for: C9H17N30SC12(286,22).Elemental analysis for: C9H17N30SC12(286.22).
Beregnet %: C 37,76; H 5,98; N 14,67Calculated %: C 37.76; H 5.98; N 14.67
Funnet: C 37,49; H,6,07; N 14,55. Found: C 37.49; H, 6.07; N 14.55.
Eksempel 14 Example 14
5-( N, N- dimetylamino) metyl- 2- tiometylfuranhydrobromid Til en oppløsning av natriummetoksyd (2,97 g; 0,055 mol) i metanol (100 ml) mettet med hydrogensulfid ble tilsatt en oppløsning av 5-(N,N-dimetylamino)metyl-2-brommetylfuranhyd-robromid (7,47 g, 0,025 mol), i metanol (30 ml).'i løpet av 30 min. ved 0°C under en samtidig gjennombobling av hydrogensulfid. 5-(N,N-dimethylamino)methyl-2-thiomethylfuran hydrobromide To a solution of sodium methoxide (2.97 g; 0.055 mol) in methanol (100 ml) saturated with hydrogen sulfide was added a solution of 5-(N,N-dimethylamino) )methyl-2-bromomethylfuran hydrobromide (7.47 g, 0.025 mol), in methanol (30 ml) over 30 min. at 0°C under a simultaneous bubbling of hydrogen sulphide.
Den resulterende oppløsning ble surgjort med en 30%-ig HBr- ; The resulting solution was acidified with a 30% HBr;
oppløsning i 2 propanol (16 ml) og deretter behandlet med i solution in 2 propanol (16 ml) and then treated with i
trekull (0,5 g). Det organiske oppløsningsmiddel ble destillert fra og den oljeaktige rest oppløst i 2-propanol. De uorganiske salter ble frafiltrert og alkoholoppløsningen ! konsentrert til et lite volum. 5,6 g av tittelforbindelsen ble erholdt, smp. 129-130°C (utbytte 90%).. IR (KBr).: 2700-2500, 1550, 1475, 1415, 1385, 1235, 1140, 1030, 1010, 980, charcoal (0.5 g). The organic solvent was distilled from and the oily residue dissolved in 2-propanol. The inorganic salts were filtered off and the alcohol solution ! concentrated to a small volume. 5.6 g of the title compound were obtained, m.p. 129-130°C (yield 90%).. IR (KBr).: 2700-2500, 1550, 1475, 1415, 1385, 1235, 1140, 1030, 1010, 980,
935, 820, 760 cm"<1>. NMR (MeOH-d4): 2,95 (s, 6H), 3,85 (s, 2H), 4,50 (s, 2H), 6,4 2 (d, 1H, J=3,5 Hz), 6,7 9 (d, 1H, J=3,5 Hz). 935, 820, 760 cm"<1>. NMR (MeOH-d4): 2.95 (s, 6H), 3.85 (s, 2H), 4.50 (s, 2H), 6.4 2 ( d, 1H, J=3.5 Hz), 6.7 9 (d, 1H, J=3.5 Hz).
Elementæranalyse for: CH., , BrNO S^ L252.18)Elemental analysis for: CH., , BrNO S^ L252.18)
Beregnet %: C 38,06; H 5,59; S 12,71 j Funnet: C 38,00; H 5,51; S 12,80. Calculated %: C 38.06; H 5.59; S 12.71 j Found: C 38.00; H 5.51; P12.80.
Eksempel 15 5-( N, N- dimetylamino) metyl- 2- tiometyl- furanhydroklorid Som beskrevet i det foregående eksempel erholdes denne forbindelse med et utbytte på 80% (4,15 g). ved å utgå fra 5-(N, N-dimetylamino)metyl-2-klorometyl-furanhydroklorid (5,25 g, 0,025 mol). Forbindelsen som smelter ved 133-134°C (fra 2-propanol) har de samme spektralegenskaper som den tidligere forbindelse. Example 15 5-(N,N-dimethylamino)methyl-2-thiomethyl-furan hydrochloride As described in the preceding example, this compound is obtained with a yield of 80% (4.15 g). starting from 5-(N,N-dimethylamino)methyl-2-chloromethyl-furan hydrochloride (5.25 g, 0.025 mol). The compound which melts at 133-134°C (from 2-propanol) has the same spectral properties as the previous compound.
Elementæranalyse for: CgH^ClNOS (207 ,68)Elemental analysis for: CgH^ClNOS (207 .68)
Beregnet %: C 46,25; H 6,79; S 15,43 Funnet: C 46,30; H 6,81; S 15,54. Calculated %: C 46.25; H 6.79; S 15.43 Found: C 46.30; H 6.81; S 15.54.
Eksempel 16 Example 16
5- ( N, N- dimetylamino), mety 1- 2- tiometylfuranhydrobromid 5-(N,N-dimetylamino)mety1-2-tioureylmetylfurandihydroklorid (28,6 g, 0,1 mol), ble oppløst i en 10% kaliumhydroksydoppløs-ning i metanol. Etter 50 min. under tilbakeløp ble oppløs-ningen avkjølt og titrert med 30%-ig hydrobromsyre i 2-propanol inntil pH 1. De uorganiske salter ble frafiltrert og oppløsningsmiddelet destillert under vakuum. Den oljeaktige rest krystalliserer ved tilsetning av acetonitril til å gi 92% av tittelforbindelsen med smp. 128-130°C. 5-(N,N-dimethylamino),methyl 1-2-thiomethylfuran hydrobromide 5-(N,N-dimethylamino)methyl-2-thioureylmethylfuran dihydrochloride (28.6 g, 0.1 mol), was dissolved in a 10% potassium hydroxide soln. ning in methanol. After 50 min. under reflux, the solution was cooled and titrated with 30% hydrobromic acid in 2-propanol until pH 1. The inorganic salts were filtered off and the solvent distilled under vacuum. The oily residue crystallizes on addition of acetonitrile to give 92% of the title compound m.p. 128-130°C.
'i ) 'l 'i ) 'l
Eksempel 17 5-( N, N- dietylamino) metyl- 2- tiometyl- furanhydrobromid Ved å utgå fra 5-(N,N-dietylamino)metyl-2-brommetylfuran- i hydrobromid (1,63 g, 5 mmol) og en natriummetoksydoppløsning i metanol (5,95 g, 11 mmol) som på forhånd var mettet med hydrogensulfid ble tittelforbindelsen erholdt med 92% utbytte (1,28 g, smp. 114-117°C), ved fremgangsmåten beskrevet i henhold til eksempel 14. ! Example 17 5-(N,N-diethylamino)methyl-2-thiomethyl-furan hydrobromide Starting from 5-(N,N-diethylamino)methyl-2-bromomethylfuran- i hydrobromide (1.63 g, 5 mmol) and a sodium methoxide solution in methanol (5.95 g, 11 mmol) which was previously saturated with hydrogen sulphide, the title compound was obtained in 92% yield (1.28 g, m.p. 114-117°C), by the method described according to example 14. !
i i i Eksempel 18 5-( N- propylamino) metyl- 2- tiometyl- furanhydroklorid Ved å hydrolysere 5-(N-propylamino)metyl-2-tioureylmetyl-furandihydroklorid (1,2 g, 4,0 mmol) i 10 ml 5%-ig mefcano-lisk oppløsning av kaliumhydroksyd under tilbakeløp i 30 min. i i i Example 18 5-(N-propylamino)methyl-2-thiomethyl-furan hydrochloride By hydrolyzing 5-(N-propylamino)methyl-2-thioureylmethyl-furan dihydrochloride (1.2 g, 4.0 mmol) in 10 ml 5% -mg mefcanolic solution of potassium hydroxide under reflux for 30 min.
i ble tittelforbindelsen erholdt med et utbytte på 96%. in the title compound was obtained with a yield of 96%.
Eksempel 19 Example 19
N-[ 2-[[[ 5-( dimetylamino)- metyl- 2- furanyl]- metyl]- tio]- etyl]-N'- metyl- 2- nitro- l, 1- etendiamin N-[ 2-[[[ 5-(dimethylamino)- methyl- 2- furanyl]- methyl]- thio]- ethyl]-N'- methyl- 2- nitro- 1, 1- ethenediamine
Til en oppløsning av 2-[[5-(dimetylamino)metyl]-2-tiometyl-furan (17,1 g, 0,1 mol) i acetonitril (120 ml) tilsettes' dråpevis ved 0°C en 5N vandig natriumhydroksydoppløsning (20,0. ml, 0,1 mol). Deretter ble tilsatt i små porsjoner 1-etylenimino-l-metylamino-2-nitroeten (14,3 g, 0,1 mol). Etter omrøring i 24 h ble oppløsningsmiddelet fradestillert og oljeresten omkrystallisert fra en aceton-cykloheksanbland-ing og det ble erholdt 25,4 g (82%) av den rene tittelforbindelse, smp. 70-72°C. IR (KBr): 3200-3300, 2980, 1620, 1590, 1540, 1335 cm"<1.>A 5N aqueous sodium hydroxide solution ( 20.0 ml, 0.1 mol). Then 1-ethyleneimino-1-methylamino-2-nitroethylene (14.3 g, 0.1 mol) was added in small portions. After stirring for 24 h, the solvent was distilled off and the oil residue recrystallized from an acetone-cyclohexane mixture and 25.4 g (82%) of the pure title compound were obtained, m.p. 70-72°C. IR (KBr): 3200-3300, 2980, 1620, 1590, 1540, 1335 cm"<1.>
NMR ( 6 i ppm): 2,3 (s, 3H), 2,5-3,6 (m, 8H), 2,4 (s, skarp, 6H), 6,4-6,9 (m, 3H). NMR ( 6 in ppm): 2.3 (s, 3H), 2.5-3.6 (m, 8H), 2.4 (s, sharp, 6H), 6.4-6.9 (m, 3H).
Elementæranalyse for: C-^<H>^<N>^<O>^<S>(314,40)Elemental analysis for: C-^<H>^<N>^<O>^<S>(314,40)
Beregnet %: C 49,66; H 7,05; N 17,82Calculated %: C 49.66; H 7.05; N 17.82
Funnet: C 49,39; H 6,89; N 17,76. Found: C 49.39; H 6.89; N 17.76.
Eksempel 20 Example 20
N- [ 2- [ [ [ 5- ( dimetylamino), metyl- 2- f uranyl] - metyl] - tio] - etyl] - ; N'- propyl- 2- nitro- etendiamin 1 i N-[2-[[[5-(dimethylamino),methyl-2-furanyl]-methyl]-thio]-ethyl]-; N'-propyl-2-nitro-ethenediamine 1 i
Til en oppløsning av 2-[[5-(dimetylamino)-metyl]-2-tiometyl-To a solution of 2-[[5-(dimethylamino)-methyl]-2-thiomethyl-
i ■ furan (3,42 g, 20,0 mmol) i metanol (60 ml) ble under omrør-• ing og i en nitrogenstrøm ved -5°C-0°C tilsatt fast KOH (1,12 g, 20,0 mmol). En oppløsning av 1-etylenimino-l-propylamino-2-ni.troeten (3,08 g, 18,0 mmol). i metanol (80 ml) ble derettér tilsatt dråpevis. Etter 14 h ved romtemperatur ble i ■ furan (3.42 g, 20.0 mmol) in methanol (60 ml) was added under stirring and in a stream of nitrogen at -5°C-0°C solid KOH (1.12 g, 20, 0 mmol). A solution of 1-ethyleneimino-1-propylamino-2-nitroethylene (3.08 g, 18.0 mmol). in methanol (80 ml) was then added dropwise. After 14 h at room temperature,
oppløsningsmiddelet avdestillert og den gjenværende olje opp-løst i 200 ml etylmetylketon, filtrert varmt på trekull og destillert inntil påbegynnende krystallisasjon. Det bleier-' holdt 5,67 g (92%) av den rene tittelforbindelse, smp. 54-56°C. IR (KBr) : 3150-3400 (bredt)., 2970, 2940, 1610, 1585, 1535, the solvent distilled off and the remaining oil dissolved in 200 ml of ethyl methyl ketone, filtered hot on charcoal and distilled until crystallization begins. There remained 5.67 g (92%) of the pure title compound, m.p. 54-56°C. IR (KBr) : 3150-3400 (broad)., 2970, 2940, 1610, 1585, 1535,
1330 cm"<1>. NMR ( S i ppm) : 2,2-3,7 (m, 15H)., 2,5 (s, skarp,, 6H), 6,5-6,9 (m, 3H). 1330 cm"<1>. NMR (S in ppm) : 2.2-3.7 (m, 15H)., 2.5 (s, sharp,, 6H), 6.5-6.9 (m, 3H).
Elementæranalyse for: C15H26N4°3S (342,25) ; Beregnet % : C 52,61; H 7,65; N 16,36 Funnet: C 52,89; H 7,92; N 16,60. Elemental analysis for: C15H26N4°3S (342.25) ; Calculated % : C 52.61; H 7.65; N 16.36 Found: C 52.89; H 7.92; N 16.60.
Eksempel 21 Example 21
N-[ 2-[[[ 5-( dimetylamino)- metyl- 2- furanyl]- metyl]- tio]- etyl]-. N-[ 2-[[[ 5-(dimethylamino)- methyl- 2- furanyl]- methyl]- thio]- ethyl]-.
N'- metyl- 2- nitroetendiaminN'-methyl-2-nitroethenediamine
Til en 2-[[5-(dimetylamino)-metyl]-2-tiometylfuran (9,42 g, 55,0 mmol) suspensjon i vann (100 ml) ble tilsatt en 5N nat-riumhydroksydoppløsning (11,6 ml, 58,0 mmol), temperaturen ble holdt i området -10°C til -5°C To a suspension of 2-[[5-(dimethylamino)methyl]-2-thiomethylfuran (9.42 g, 55.0 mmol) in water (100 mL) was added a 5N sodium hydroxide solution (11.6 mL, 58 .0 mmol), the temperature was kept in the range -10°C to -5°C
Deretter ble tilsatt l-etylenimino-l-metylamino-2-nitroeten (7,87 g, 55,0 mmol). i små porsjoner i løpet av 30 min. Etter 6 h ved -5°C ble oppløsningen oppvarmet til romtemperatur og deretter omrørt i 18 h. Then 1-ethyleneimino-1-methylamino-2-nitroethylene (7.87 g, 55.0 mmol) was added. in small portions within 30 min. After 6 h at -5°C, the solution was warmed to room temperature and then stirred for 18 h.
Det således erholdte presipitat ble oppsamlet på ét filter, vasket med vann og oppløst i metylisobutylketon og filtrert o varmt med trekull. Ved inndampning av den klare oppløsning utkrystalliserte tittelforbindelsen til å gi 13,6 g (79 %) smp. 70-73°C. The precipitate thus obtained was collected on a filter, washed with water and dissolved in methyl isobutyl ketone and filtered hot with charcoal. Evaporation of the clear solution crystallized the title compound to give 13.6 g (79%) m.p. 70-73°C.
I IN
Eksempel 22 N-[ 2-[[[ 5-( dimetylamino)- metyl- 2- furanyl]- metyl]- tio]- etyl]-j N'- metyl- 2- nitroetendiamin Reaksjonen ble utført i dimetylformamid (40 ml) ved å utgå i fra 2-[5-(dimetylamino)-metyl]-2-tiometylfuran (1,71 g, 10,0; mmol) og l-etylenimirio-l-métylamino-2-nitroeten (1,43 g, \<;>'10,0 mmol). ' Gjenvinningen av tittelforbindelsen ble utført ved fremgangsmåten ifølge eksempel 19. ! j 2,7 6 g (88%) av det rene produkt ble erholdt med et smelte- , punkt på 71-7 3°C. ! Example 22 N-[ 2-[[[ 5-(dimethylamino)-methyl-2-furanyl]-methyl]-thio]-ethyl]-j N'-methyl-2-nitroethenediamine The reaction was carried out in dimethylformamide (40 ml) by starting from 2-[5-(dimethylamino)methyl]-2-thiomethylfuran (1.71 g, 10.0; mmol) and l-ethyleneimirio-l-methylamino-2-nitroethylene (1.43 g, \<;>'10.0 mmol). The recovery of the title compound was carried out by the method of Example 19. j 2.76 g (88%) of the pure product was obtained with a melting point of 71-73°C. !
Som beskrevet i dette eksempel og ved. å velge passende N- j dialkylamino-metyl-2-tiometylfuraner og 1-etylenimino-l-alkylamino-2-nitroetener ble de følgende forbindelser erholdt: - N-[2-[[[5-dimetylamino)-metyl-2-furanyl]-metyl]-tio]-etyl]-N<1->mety1-2-nitro-l,1-etendiamin, smp. 124-126°C. Elementæranalyse for: C, CH« ,-N .0-S (342,45) J lb 2 6 43j Beregnet %: C 52,61; H 7,65; N 16,36 Funnet %: C 52,38; H 7,41; N 16,09. j - N- [2- [[ [5-(dimetylamino).-metyl-2-furanyl] -metyl]-tio] - etyl]-N'-etyl-2-nitro-l,1-etendiamin, smp. 141-144°C. As described in this example and by. choosing appropriate N-j dialkylamino-methyl-2-thiomethylfurans and 1-ethyleneimino-1-alkylamino-2-nitroethenes, the following compounds were obtained: - N-[2-[[[5-dimethylamino)-methyl-2-furanyl ]-methyl]-thio]-ethyl]-N<1->methyl-2-nitro-1,1-ethenediamine, m.p. 124-126°C. Elemental analysis for: C, CH« ,-N .0-S (342.45) J lb 2 6 43j Calculated %: C 52.61; H 7.65; N 16.36 Found %: C 52.38; H 7.41; N 16.09. j - N- [2- [[ [5-(dimethylamino).-methyl-2-furanyl]-methyl]-thio]-ethyl]-N'-ethyl-2-nitro-1,1-ethenediamine, m.p. 141-144°C.
Elementæranalyse for: C16<H>2<gN>403S (356,48).Elemental analysis for: C16<H>2<gN>403S (356.48).
Beregnet %: C 53,90; H 7,92; N 15,72Calculated %: C 53.90; H 7.92; N 15.72
Funnet %: C 53,63; H 7,82; N 16,01. Found %: C 53.63; H 7.82; N 16.01.
Claims (4)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT22006/80A IT1151010B (en) | 1980-05-13 | 1980-05-13 | METHOD FOR THE PREPARATION OF NI-2-5-DIMETHYLAMINE-METHYL-2-FURANYL-METHYL-THIO-ETHYL-N'-ALCHIL-2-NITRO-1,1-ETHYDIAMINE |
IT25156/80A IT1132918B (en) | 1980-10-07 | 1980-10-07 | 1-ETHYLENIMINO-1-ALCHILAMINO-2-NITRO ETHENES AND PROCESS FOR THEIR PREPARATION |
IT26158/80A IT1134408B (en) | 1980-11-21 | 1980-11-21 | METHOD FOR THE PREPARATION OF 2-THYOMETHY-FURANI 5-REPLACED AND COMPOUNDS SO OBTAINED |
Publications (1)
Publication Number | Publication Date |
---|---|
NO811501L true NO811501L (en) | 1981-11-16 |
Family
ID=27273236
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO811501A NO811501L (en) | 1980-05-13 | 1981-05-04 | PROCEDURE FOR THE PREPARATION OF ETHENDIAMINE DERIVATIVES, AND INTERMEDIATES FOR THESE |
Country Status (10)
Country | Link |
---|---|
DE (1) | DE3118813A1 (en) |
DK (1) | DK211881A (en) |
ES (1) | ES502121A0 (en) |
FI (1) | FI811376L (en) |
FR (1) | FR2482595A1 (en) |
GB (1) | GB2075980A (en) |
GR (1) | GR74914B (en) |
NL (1) | NL8102334A (en) |
NO (1) | NO811501L (en) |
SE (1) | SE8102985L (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT72320B (en) * | 1980-01-08 | 1982-07-23 | Glaxo Group Ltd | Process for preparation of a furan derivative |
US4590192A (en) * | 1982-10-01 | 1986-05-20 | Beecham Group P.L.C. | Benzisothiazoles, their pharmaceutical compositions, and method of use |
US4558044A (en) * | 1983-02-19 | 1985-12-10 | Beecham Group P.L.C. | 1,2,4-Benzothiadiazines |
SU1384197A3 (en) * | 1983-07-15 | 1988-03-23 | Рихтер Гедеон Ведьесети Дьяр Рт (Инопредприятие) | Method of producing 1-[2-(5-(dimethylaminomethyl)-2-(furylmethylthio)-ethyl)] amino-1-(methylamino)-2-nitroethylene or its hydrochloride and method of producing dehydrochloride 2-(2-aminoethyl)-thiomethyl-5-(dimethylaminomethyl) - furan or its monohydrochloride |
CN114605360B (en) * | 2022-03-09 | 2023-05-05 | 河北海力恒远新材料股份有限公司 | Preparation method of 2- [ [ [5- (dimethylamino) methyl-2-furyl ] methyl ] thio ] ethylamine |
-
1981
- 1981-05-04 NO NO811501A patent/NO811501L/en unknown
- 1981-05-04 FI FI811376A patent/FI811376L/en not_active Application Discontinuation
- 1981-05-11 GR GR64932A patent/GR74914B/el unknown
- 1981-05-12 ES ES502121A patent/ES502121A0/en active Granted
- 1981-05-12 SE SE8102985A patent/SE8102985L/en not_active Application Discontinuation
- 1981-05-12 NL NL8102334A patent/NL8102334A/en not_active Application Discontinuation
- 1981-05-12 DE DE19813118813 patent/DE3118813A1/en not_active Ceased
- 1981-05-13 GB GB8114575A patent/GB2075980A/en not_active Withdrawn
- 1981-05-13 DK DK211881A patent/DK211881A/en unknown
- 1981-05-13 FR FR8109547A patent/FR2482595A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
ES8207523A1 (en) | 1982-10-01 |
ES502121A0 (en) | 1982-10-01 |
DE3118813A1 (en) | 1982-02-25 |
FR2482595A1 (en) | 1981-11-20 |
DK211881A (en) | 1981-11-14 |
GB2075980A (en) | 1981-11-25 |
GR74914B (en) | 1984-07-12 |
FI811376L (en) | 1981-11-14 |
SE8102985L (en) | 1981-11-14 |
NL8102334A (en) | 1981-12-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0040696B1 (en) | Aminothiadiazoles as gastric secretion inhibitors | |
CN108440345B (en) | Preparation method of sulfonamide compound | |
NO811501L (en) | PROCEDURE FOR THE PREPARATION OF ETHENDIAMINE DERIVATIVES, AND INTERMEDIATES FOR THESE | |
EP0322335A1 (en) | New-quanidino-thiazol compounds, their preparation, and use as intermediates of famotidine process | |
US7288652B2 (en) | Method for preparing oltipraz | |
NO177821B (en) | Process for Preparation of Amidoxime Derivatives | |
EP0277842A1 (en) | Aromatic amine derivatives | |
EP0095104B1 (en) | Process for the preparation of pyridyl and quinolyl imidazolinones | |
EP0298752B1 (en) | Mercapto-substituted pyridine compounds and process for preparing the same | |
EP0140335B1 (en) | Novel method of producing 1,2,3-trithiane compounds | |
CN111072656B (en) | Praziquantel synthesis method | |
CA2046293C (en) | Preparation of substituted ethenes | |
WO1989006230A1 (en) | Cyano-dienes, halopyridines, intermediates and a process for their preparation | |
US4540794A (en) | Method for preparing 5-mercapto-1,2,3-thiadiazole salts | |
CN113896722B (en) | Benzamide compound containing thiadiazole group and preparation method and application thereof | |
EP0219225B1 (en) | Process for the preparation of ranitidine or acid addition salts thereof, and intermediates for this preparation | |
EP0103840B1 (en) | Method for preparing 1,2,3-trihetero 5-membered heterocyclic compounds | |
JP3551735B2 (en) | Method for producing optically active azetidine-2-carboxylic acid | |
FR2491068A1 (en) | Prepn. of nitro-ethylene derivs. with antiulcer activity - from new 5-aminomethyl-furfuryl mercaptan and 1-amino-1-aziridinyl-2-nitro-ethylene derivs. | |
EP0066440B1 (en) | Chemical process | |
KR810000687B1 (en) | Process for heterocyclic compound | |
NO832654L (en) | PROCEDURE FOR THE PREPARATION OF NEW COMPOUNDS COMBINING INHIBITIVE EFFECTS AGAINST ANGIOTENS INJECTIVE ENZYM WITH DIURETIC EFFECTS | |
KR900003399B1 (en) | Process for preapring pyridyl and quinolyl imidazolinones | |
CN116253690A (en) | Triazole derivative and preparation method thereof | |
KR870000448B1 (en) | Process for preparing aminoalkyl furan derivatives |