JPS6354714B2 - - Google Patents
Info
- Publication number
- JPS6354714B2 JPS6354714B2 JP54147177A JP14717779A JPS6354714B2 JP S6354714 B2 JPS6354714 B2 JP S6354714B2 JP 54147177 A JP54147177 A JP 54147177A JP 14717779 A JP14717779 A JP 14717779A JP S6354714 B2 JPS6354714 B2 JP S6354714B2
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- group
- general formula
- halogen
- imidazolin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- -1 alkyl mercaptan Chemical compound 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000004414 alkyl thio group Chemical group 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 7
- 238000009835 boiling Methods 0.000 claims description 7
- OIARYBGUYNKKOW-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)pyrimidin-2-amine Chemical class C1=NC(N)=NC=C1C1=NCCN1 OIARYBGUYNKKOW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 4
- WPNJAUFVNXKLIM-UHFFFAOYSA-N Moxonidine Chemical compound COC1=NC(C)=NC(Cl)=C1NC1=NCCN1 WPNJAUFVNXKLIM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 241000726103 Atta Species 0.000 claims 2
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 0.000 claims 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 1
- BUSBKABBRVUHFS-UHFFFAOYSA-N N-(4,5-dihydroimidazol-1-yl)pyrimidin-2-amine Chemical compound N1(C=NCC1)NC1=NC=CC=N1 BUSBKABBRVUHFS-UHFFFAOYSA-N 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000002636 imidazolinyl group Chemical group 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 238000002844 melting Methods 0.000 description 33
- 230000008018 melting Effects 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000005005 aminopyrimidines Chemical group 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 7
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 7
- CMSOCLHYOTXEHM-UHFFFAOYSA-N 1-[2-(1-amino-4,6-dichloro-2-methyl-2h-pyrimidin-5-yl)-4,5-dihydroimidazol-1-yl]ethanone Chemical compound NN1C(C)N=C(Cl)C(C=2N(CCN=2)C(C)=O)=C1Cl CMSOCLHYOTXEHM-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000001589 carboacyl group Chemical group 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- OAIPRQSPYGPMAG-UHFFFAOYSA-N 4,6-dichloro-2-cyclopropylpyrimidin-5-amine Chemical compound N1=C(Cl)C(N)=C(Cl)N=C1C1CC1 OAIPRQSPYGPMAG-UHFFFAOYSA-N 0.000 description 3
- KATIQOPFTJLEKZ-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-4-methoxy-2-methyl-6-methylsulfanyl-2h-pyrimidin-1-amine Chemical compound COC1=NC(C)N(N)C(SC)=C1C1=NCCN1 KATIQOPFTJLEKZ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- VFGWJXCRWXZRHV-UHFFFAOYSA-N 2-cyclopropyl-4-hydroxy-1h-pyrimidin-6-one Chemical compound OC1=CC(O)=NC(C2CC2)=N1 VFGWJXCRWXZRHV-UHFFFAOYSA-N 0.000 description 2
- LODQXLJNUJXOHS-UHFFFAOYSA-N 2-cyclopropyl-4-hydroxy-5-nitro-1h-pyrimidin-6-one Chemical compound OC1=C([N+]([O-])=O)C(O)=NC(C2CC2)=N1 LODQXLJNUJXOHS-UHFFFAOYSA-N 0.000 description 2
- GWPBQZTUTVJCHO-UHFFFAOYSA-N 2-cyclopropyl-5-(4,5-dihydro-1h-imidazol-2-yl)-4,6-dimethoxy-2h-pyrimidin-1-amine Chemical compound NN1C(OC)=C(C=2NCCN=2)C(OC)=NC1C1CC1 GWPBQZTUTVJCHO-UHFFFAOYSA-N 0.000 description 2
- UQOKRDJILZMZKU-UHFFFAOYSA-N 2-nitropyrimidine Chemical compound [O-][N+](=O)C1=NC=CC=N1 UQOKRDJILZMZKU-UHFFFAOYSA-N 0.000 description 2
- FKRXXAMAHOGYNT-UHFFFAOYSA-N 4,6-dichloro-2-methylpyrimidin-5-amine Chemical compound CC1=NC(Cl)=C(N)C(Cl)=N1 FKRXXAMAHOGYNT-UHFFFAOYSA-N 0.000 description 2
- PWAPAZNVFQZPMY-UHFFFAOYSA-N 4-chloro-2-cyclopropyl-5-(4,5-dihydro-1h-imidazol-2-yl)-6-methoxy-2h-pyrimidin-1-amine Chemical compound ClC1=NC(C2CC2)N(N)C(OC)=C1C1=NCCN1 PWAPAZNVFQZPMY-UHFFFAOYSA-N 0.000 description 2
- OEMPTJPXOCCVPP-UHFFFAOYSA-N 4-chloro-5-(4,5-dihydro-1h-imidazol-2-yl)-2-methyl-6-methylsulfanyl-2h-pyrimidin-1-amine Chemical compound ClC1=NC(C)N(N)C(SC)=C1C1=NCCN1 OEMPTJPXOCCVPP-UHFFFAOYSA-N 0.000 description 2
- BFOJCRMEMULDMK-UHFFFAOYSA-N 4-chloro-5-(4,5-dihydro-1h-imidazol-2-yl)-6-ethoxy-2-methyl-2h-pyrimidin-1-amine Chemical compound ClC1=NC(C)N(N)C(OCC)=C1C1=NCCN1 BFOJCRMEMULDMK-UHFFFAOYSA-N 0.000 description 2
- GVOLMMVWBFBMMF-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-4,6-dimethoxypyrimidin-2-amine Chemical compound COC1=NC(N)=NC(OC)=C1C1=NCCN1 GVOLMMVWBFBMMF-UHFFFAOYSA-N 0.000 description 2
- 150000005008 5-aminopyrimidines Chemical class 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 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 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- KRZGKJJPEOUIBI-UHFFFAOYSA-N hydron;thiourea;iodide Chemical compound I.NC(S)=N KRZGKJJPEOUIBI-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical class CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- DQMWMUMCNOJLSI-UHFFFAOYSA-N n-carbamothioylbenzamide Chemical compound NC(=S)NC(=O)C1=CC=CC=C1 DQMWMUMCNOJLSI-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- OPVZXRFEXUBROJ-UHFFFAOYSA-N (4,6-dimethoxypyrimidin-5-yl)thiourea Chemical compound COC1=NC=NC(OC)=C1NC(N)=S OPVZXRFEXUBROJ-UHFFFAOYSA-N 0.000 description 1
- FNAOWXNMAKVAIP-UHFFFAOYSA-N 1-[2-(1-amino-4,6-dichloro-2-cyclopropyl-2h-pyrimidin-5-yl)-4,5-dihydroimidazol-1-yl]ethanone Chemical compound CC(=O)N1CCN=C1C1=C(Cl)N(N)C(C2CC2)N=C1Cl FNAOWXNMAKVAIP-UHFFFAOYSA-N 0.000 description 1
- KVMGOOSNGQIZCT-UHFFFAOYSA-N 1-[2-(2-amino-4,6-dichloropyrimidin-5-yl)-4,5-dihydroimidazol-1-yl]ethanone Chemical compound CC(=O)N1CCN=C1C1=C(Cl)N=C(N)N=C1Cl KVMGOOSNGQIZCT-UHFFFAOYSA-N 0.000 description 1
- KEVRHVMWBKFGLO-UHFFFAOYSA-N 2,4-dimethoxypyrimidine Chemical compound COC1=CC=NC(OC)=N1 KEVRHVMWBKFGLO-UHFFFAOYSA-N 0.000 description 1
- HOCFRZXMVTXATD-UHFFFAOYSA-N 2-cyclopropyl-5-(4,5-dihydro-1h-imidazol-2-yl)-4,6-bis(methylsulfanyl)-2h-pyrimidin-1-amine Chemical compound NN1C(SC)=C(C=2NCCN=2)C(SC)=NC1C1CC1 HOCFRZXMVTXATD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XCAAKLMJGXTCMA-UHFFFAOYSA-N 4,6-dichloro-2-cyclopropyl-5-nitropyrimidine Chemical compound N1=C(Cl)C([N+](=O)[O-])=C(Cl)N=C1C1CC1 XCAAKLMJGXTCMA-UHFFFAOYSA-N 0.000 description 1
- NMQWSFISZWSJDX-UHFFFAOYSA-N 4,6-dichloro-5-(4,5-dihydro-1h-imidazol-2-yl)pyrimidin-2-amine Chemical compound ClC1=NC(N)=NC(Cl)=C1C1=NCCN1 NMQWSFISZWSJDX-UHFFFAOYSA-N 0.000 description 1
- OENDOJDJDYXZJR-UHFFFAOYSA-N 4-(4,5-dihydro-1H-imidazol-2-yl)pyrimidin-2-amine Chemical compound N1C(=NCC1)C1=NC(=NC=C1)N OENDOJDJDYXZJR-UHFFFAOYSA-N 0.000 description 1
- VIVONSUVAHDRLB-UHFFFAOYSA-N 4-chloro-5-(4,5-dihydro-1h-imidazol-2-yl)-6-methoxy-2-methyl-2h-pyrimidin-1-amine Chemical compound ClC1=NC(C)N(N)C(OC)=C1C1=NCCN1 VIVONSUVAHDRLB-UHFFFAOYSA-N 0.000 description 1
- ZJEGAEBMGRVMJD-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-2,6-dimethoxypyrimidin-4-amine Chemical compound COC1=NC(OC)=NC(N)=C1C1=NCCN1 ZJEGAEBMGRVMJD-UHFFFAOYSA-N 0.000 description 1
- GMPGXIMAOQBRHN-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-4,6-diethoxypyrimidin-2-amine Chemical compound CCOC1=NC(N)=NC(OCC)=C1C1=NCCN1 GMPGXIMAOQBRHN-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- WLLGXSLBOPFWQV-UHFFFAOYSA-N MGK 264 Chemical compound C1=CC2CC1C1C2C(=O)N(CC(CC)CCCC)C1=O WLLGXSLBOPFWQV-UHFFFAOYSA-N 0.000 description 1
- RKAHSAWADCFIMX-UHFFFAOYSA-N NC(N)=S.C1=CN=CN=C1 Chemical class NC(N)=S.C1=CN=CN=C1 RKAHSAWADCFIMX-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- PMEJIFXRYZEOTM-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(2,4-dimethoxypyrimidin-5-yl)azanium;iodide Chemical compound [I-].COC1=NC=C([NH+]=C(N)SC)C(OC)=N1 PMEJIFXRYZEOTM-UHFFFAOYSA-N 0.000 description 1
- IVZHAGHNBCEAIG-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(4,6-diethoxypyrimidin-5-yl)azanium;iodide Chemical compound [I-].CCOC1=NC=NC(OCC)=C1[NH+]=C(N)SC IVZHAGHNBCEAIG-UHFFFAOYSA-N 0.000 description 1
- QQYXGRQTVJLPHY-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(4,6-dimethoxypyrimidin-5-yl)azanium;iodide Chemical compound [I-].COC1=NC=NC(OC)=C1[NH+]=C(N)SC QQYXGRQTVJLPHY-UHFFFAOYSA-N 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 1
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate 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
- 239000000155 melt Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005406 washing Methods 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
- C07D239/30—Halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2849537A DE2849537C2 (de) | 1978-11-15 | 1978-11-15 | Substituierte 5-(2-Imidazolin-2-yl)-aminopyrimidine, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5592383A JPS5592383A (en) | 1980-07-12 |
JPS6354714B2 true JPS6354714B2 (xx) | 1988-10-28 |
Family
ID=6054732
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP14717779A Granted JPS5592383A (en) | 1978-11-15 | 1979-11-15 | Novel substituted 55*22imidazolinee22yl** aminopyrimidine*its manufacture and its use as drug |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS5592383A (xx) |
BE (1) | BE880042A (xx) |
DE (1) | DE2849537C2 (xx) |
ZA (1) | ZA796148B (xx) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3016767A1 (de) * | 1980-04-30 | 1981-11-05 | Beiersdorf Ag, 2000 Hamburg | Pyrimidylthioharnstoffe, diese enthaltende arzneimittel und deren verwendung |
DE3423293C2 (de) * | 1984-06-23 | 1995-08-24 | Lohmann Therapie Syst Lts | Selbstklebendes Pflaster |
DE3423328A1 (de) * | 1984-06-23 | 1986-01-02 | Beiersdorf Ag, 2000 Hamburg | Selbstklebendes pflaster |
DE4423177A1 (de) * | 1994-07-01 | 1996-01-04 | Kali Chemie Pharma Gmbh | Antihyperglykämisch wirksame Arzneimittel |
DE19911371A1 (de) | 1999-03-15 | 2000-09-21 | Solvay Pharm Gmbh | Arzneimittel zur Behandlung von funktionellen Störungen und Erkrankungen der unteren Darmwege, insbesondere von damit einhergehenden abdominalen visceralen Schmerzen |
PL372695A1 (en) | 2002-06-19 | 2005-07-25 | Solvay Pharmaceuticals Gmbh | Medicament for the treatment of diseases requiring inhibition or a reduction in the activity of ph value-regulating bicarbonate transporter proteins |
AU2007213887A1 (en) * | 2006-01-27 | 2007-08-16 | F. Hoffmann-La Roche Ag | Use of 2-imidazoles for the treatment of CNS disorders |
ATE407931T1 (de) * | 2006-06-26 | 2008-09-15 | Chemagis Ltd | Verbessertes verfahren zur herstellung von moxonidine |
BRPI0806940A2 (pt) | 2007-02-02 | 2014-05-06 | Hoffmann La Roche | 2-amino-oxazolinas como ligantes taar1 para distúrbios do snc |
MX2009008465A (es) | 2007-02-15 | 2009-08-20 | Hoffmann La Roche | Nuevas 2-aminooxazolinas como ligandos de taar1. |
US8242153B2 (en) | 2008-07-24 | 2012-08-14 | Hoffmann-La Roche Inc. | 4,5-dihydro-oxazol-2YL derivatives |
US8354441B2 (en) | 2009-11-11 | 2013-01-15 | Hoffmann-La Roche Inc. | Oxazoline derivatives |
US9452980B2 (en) | 2009-12-22 | 2016-09-27 | Hoffmann-La Roche Inc. | Substituted benzamides |
DE102012215896A1 (de) | 2012-09-07 | 2014-03-13 | Wörwag Pharma GmbH & Co.KG | Moxonidinsynthese mit Hilfe organischer Basen |
ES2608004T3 (es) | 2012-12-03 | 2017-04-05 | WÖRWAG PHARMA GmbH & Co. KG | Método mediante catálisis por transferencia de fase |
EP2765131B1 (en) | 2013-02-08 | 2016-11-23 | Arevipharma GmbH | Process for the production of Moxonidine |
BR112018015389B1 (pt) | 2016-03-17 | 2023-12-19 | F. Hoffmann-La Roche Ag | Derivado de 5-etil-4-metil-pirazol-3-carboxamida, seu processo de fabricação, preparação farmacêutica oral e uso |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE754832A (fr) * | 1969-08-14 | 1971-02-15 | Beecham Group Ltd | Iminazolines |
BE503170A (xx) * | 1975-09-02 |
-
1978
- 1978-11-15 DE DE2849537A patent/DE2849537C2/de not_active Expired
-
1979
- 1979-11-14 BE BE0/198116A patent/BE880042A/fr not_active IP Right Cessation
- 1979-11-15 JP JP14717779A patent/JPS5592383A/ja active Granted
- 1979-11-15 ZA ZA00796148A patent/ZA796148B/xx unknown
Also Published As
Publication number | Publication date |
---|---|
DE2849537C2 (de) | 1983-03-17 |
BE880042A (fr) | 1980-05-14 |
JPS5592383A (en) | 1980-07-12 |
DE2849537A1 (de) | 1980-05-22 |
ZA796148B (en) | 1980-11-26 |
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