CS203995B2 - Method of producing heterocyclic compounds - Google Patents
Method of producing heterocyclic compounds Download PDFInfo
- Publication number
- CS203995B2 CS203995B2 CS768760A CS876076A CS203995B2 CS 203995 B2 CS203995 B2 CS 203995B2 CS 768760 A CS768760 A CS 768760A CS 876076 A CS876076 A CS 876076A CS 203995 B2 CS203995 B2 CS 203995B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methyl
- pyrimidone
- pyridylmethyl
- mixture
- pyridyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 29
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 150000001412 amines Chemical class 0.000 claims abstract description 5
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical class NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 4-imidazolyl ring Chemical group 0.000 claims description 38
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 35
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000938 histamine H1 antagonist Substances 0.000 abstract 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 abstract 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 20
- 229960000583 acetic acid Drugs 0.000 description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 12
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 11
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 9
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- 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 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- WAIHMWWSWLOHNH-UHFFFAOYSA-N 2-(1,3-thiazol-2-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC1=NC=CS1 WAIHMWWSWLOHNH-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- 239000000739 antihistaminic agent Substances 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- UMCHIQCDVOOJLO-UHFFFAOYSA-N 2-[(3-bromopyridin-2-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC1=NC=CC=C1Br UMCHIQCDVOOJLO-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
- CDXLMOHXDMHKOQ-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-4-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=NC=C1 CDXLMOHXDMHKOQ-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- DADQIFJRAOADQS-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-2-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=CC=N1 DADQIFJRAOADQS-UHFFFAOYSA-N 0.000 description 3
- OKERYJZDTINJGP-UHFFFAOYSA-N 4-(3-chloropyridin-2-yl)butan-1-amine Chemical compound NCCCCC1=NC=CC=C1Cl OKERYJZDTINJGP-UHFFFAOYSA-N 0.000 description 3
- FZLICDPECGYZOF-UHFFFAOYSA-N 4-(3-ethoxypyridin-2-yl)butan-1-amine Chemical compound CCOC1=CC=CN=C1CCCCN FZLICDPECGYZOF-UHFFFAOYSA-N 0.000 description 3
- CTAIEPPAOULMFY-UHFFFAOYSA-N 6-methoxypyridine-3-carbaldehyde Chemical compound COC1=CC=C(C=O)C=N1 CTAIEPPAOULMFY-UHFFFAOYSA-N 0.000 description 3
- UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- ZNEYACZYGQIIBD-UHFFFAOYSA-N 2-(4-aminobutyl)pyridin-3-amine Chemical compound NCCCCC1=NC=CC=C1N ZNEYACZYGQIIBD-UHFFFAOYSA-N 0.000 description 2
- ZEJHNAWMJMJMCZ-UHFFFAOYSA-N 2-chloro-5,6-dimethylpyridine-3-carbaldehyde Chemical compound CC1=CC(C=O)=C(Cl)N=C1C ZEJHNAWMJMJMCZ-UHFFFAOYSA-N 0.000 description 2
- BYVPJDZJIHOUHA-UHFFFAOYSA-N 2-chloro-5,6-dimethylpyridine-3-carbonitrile Chemical compound CC1=CC(C#N)=C(Cl)N=C1C BYVPJDZJIHOUHA-UHFFFAOYSA-N 0.000 description 2
- VOCKNCWQVHJMAE-UHFFFAOYSA-N 2-methoxypyridine-4-carbaldehyde Chemical compound COC1=CC(C=O)=CC=N1 VOCKNCWQVHJMAE-UHFFFAOYSA-N 0.000 description 2
- NZAZWLSRKMDRNS-UHFFFAOYSA-N 2-methoxypyridine-4-carbonitrile Chemical compound COC1=CC(C#N)=CC=N1 NZAZWLSRKMDRNS-UHFFFAOYSA-N 0.000 description 2
- KZRZMQRVMQVELJ-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=CN=C1 KZRZMQRVMQVELJ-UHFFFAOYSA-N 0.000 description 2
- ACEZBZGYTQQHLL-UHFFFAOYSA-N 2-methylsulfanyl-5-(thiophen-2-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=CS1 ACEZBZGYTQQHLL-UHFFFAOYSA-N 0.000 description 2
- JKLLJHVEAMNKJV-UHFFFAOYSA-N 2-sulfanylidene-5-(thiophen-2-ylmethyl)-1h-pyrimidin-4-one Chemical compound O=C1NC(=S)NC=C1CC1=CC=CS1 JKLLJHVEAMNKJV-UHFFFAOYSA-N 0.000 description 2
- DYBCZGAECZNGOJ-UHFFFAOYSA-N 4-(3-aminopyridin-2-yl)butanenitrile Chemical compound NC1=CC=CN=C1CCCC#N DYBCZGAECZNGOJ-UHFFFAOYSA-N 0.000 description 2
- XMLZZXNLTIVKDH-UHFFFAOYSA-N 4-(3-methoxypyridin-2-yl)butan-1-amine Chemical compound COC1=CC=CN=C1CCCCN XMLZZXNLTIVKDH-UHFFFAOYSA-N 0.000 description 2
- XFZLAEXVWQCHMU-UHFFFAOYSA-N 4-(5-methyl-1h-imidazol-4-yl)butan-1-amine Chemical compound CC=1NC=NC=1CCCCN XFZLAEXVWQCHMU-UHFFFAOYSA-N 0.000 description 2
- BUGNNHLZTBPABI-UHFFFAOYSA-N 5,6-dimethyl-2-oxo-1h-pyridine-3-carbonitrile Chemical compound CC=1C=C(C#N)C(=O)NC=1C BUGNNHLZTBPABI-UHFFFAOYSA-N 0.000 description 2
- ZGQMZSLCKZISPS-UHFFFAOYSA-N 5-(pyridin-2-ylmethyl)-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound O=C1NC(=S)NC=C1CC1=CC=CC=N1 ZGQMZSLCKZISPS-UHFFFAOYSA-N 0.000 description 2
- CUIGMTBOVADTRB-UHFFFAOYSA-N 5-(pyridin-3-ylmethyl)-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound O=C1NC(=S)NC=C1CC1=CC=CN=C1 CUIGMTBOVADTRB-UHFFFAOYSA-N 0.000 description 2
- PEECAXUIEQWNMW-UHFFFAOYSA-N 5-(pyridin-4-ylmethyl)-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound O=C1NC(=S)NC=C1CC1=CC=NC=C1 PEECAXUIEQWNMW-UHFFFAOYSA-N 0.000 description 2
- FEQKZDDVINUMPR-UHFFFAOYSA-N 5-[(6-methylpyridin-3-yl)methyl]-2-methylsulfanyl-1h-pyrimidin-6-one Chemical compound N1C(SC)=NC(=O)C(CC=2C=NC(C)=CC=2)=C1 FEQKZDDVINUMPR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 2
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000006309 butyl amino group Chemical group 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- MJQIKGNOUNINSS-UHFFFAOYSA-N ethyl 3-(1,3-thiazol-2-yl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=NC=CS1 MJQIKGNOUNINSS-UHFFFAOYSA-N 0.000 description 2
- ZURUNHBLOGXHCQ-UHFFFAOYSA-N ethyl 3-(5,6-dimethylpyridin-3-yl)propanoate Chemical compound CCOC(=O)CCC1=CN=C(C)C(C)=C1 ZURUNHBLOGXHCQ-UHFFFAOYSA-N 0.000 description 2
- ZABMIGDVOIATQB-UHFFFAOYSA-N ethyl 3-(6-methylpyridin-3-yl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(C)N=C1 ZABMIGDVOIATQB-UHFFFAOYSA-N 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- VNFVKWMKVDOSKT-LREBCSMRSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;piperazine Chemical compound C1CNCCN1.OC(=O)[C@H](O)[C@@H](O)C(O)=O VNFVKWMKVDOSKT-LREBCSMRSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- HDQQOCDJJDAEPU-UHFFFAOYSA-N 2-(6-methylpyridin-3-yl)prop-2-enoic acid Chemical compound CC1=CC=C(C=N1)C(C(=O)O)=C HDQQOCDJJDAEPU-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- HTABEAIBEITBJS-UHFFFAOYSA-N 2-[(3-chloropyridin-2-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC1=NC=CC=C1Cl HTABEAIBEITBJS-UHFFFAOYSA-N 0.000 description 1
- PBMMIUUMAXTAJD-UHFFFAOYSA-N 2-[(3-fluoropyridin-2-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC1=NC=CC=C1F PBMMIUUMAXTAJD-UHFFFAOYSA-N 0.000 description 1
- SKTYIFIVFLNTCA-UHFFFAOYSA-N 2-[(3-iodopyridin-2-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC1=NC=CC=C1I SKTYIFIVFLNTCA-UHFFFAOYSA-N 0.000 description 1
- VGMZAKKUIGITCD-UHFFFAOYSA-N 2-[(3-methoxypyridin-2-yl)methylsulfanyl]ethanamine Chemical compound COC1=CC=CN=C1CSCCN VGMZAKKUIGITCD-UHFFFAOYSA-N 0.000 description 1
- SDTBFMITSFWSSR-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-5-(pyridin-2-ylmethyl)-1h-pyrimidin-6-one;trihydrobromide Chemical compound Br.Br.Br.BrC1=CC=CN=C1CSCCNC(NC1=O)=NC=C1CC1=CC=CC=N1 SDTBFMITSFWSSR-UHFFFAOYSA-N 0.000 description 1
- FANONQPHTHZJOA-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one;trihydrobromide Chemical compound Br.Br.Br.BrC1=CC=CN=C1CSCCNC(NC1=O)=NC=C1CC1=CC=CN=C1 FANONQPHTHZJOA-UHFFFAOYSA-N 0.000 description 1
- OYDQNYJYOOQUDY-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-5-(pyridin-4-ylmethyl)-1H-pyrimidin-6-one dihydrochloride Chemical compound Cl.Cl.BrC1=CC=CN=C1CSCCNC(NC1=O)=NC=C1CC1=CC=NC=C1 OYDQNYJYOOQUDY-UHFFFAOYSA-N 0.000 description 1
- MTJTUDISRVAECN-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-5-[(5,6-dimethylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound N1=C(C)C(C)=CC(CC=2C(NC(NCCSCC=3C(=CC=CN=3)Br)=NC=2)=O)=C1 MTJTUDISRVAECN-UHFFFAOYSA-N 0.000 description 1
- NYDBUAOXTSYPNN-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one;trihydrochloride Chemical compound Cl.Cl.Cl.C1=NC(C)=CC=C1CC(C(N1)=O)=CN=C1NCCSCC1=NC=CC=C1Br NYDBUAOXTSYPNN-UHFFFAOYSA-N 0.000 description 1
- BZGIWKRMWCEQGJ-UHFFFAOYSA-N 2-[2-[(3-bromopyridin-2-yl)methylsulfanyl]ethylamino]-6-methyl-5-(pyridin-3-ylmethyl)-1h-pyrimidin-4-one Chemical compound N1C(=O)C(CC=2C=NC=CC=2)=C(C)N=C1NCCSCC1=NC=CC=C1Br BZGIWKRMWCEQGJ-UHFFFAOYSA-N 0.000 description 1
- ATAQPWJXJCSDKK-UHFFFAOYSA-N 2-[2-[(3-chloropyridin-2-yl)methylsulfanyl]ethylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound ClC1=CC=CN=C1CSCCNC(NC1=O)=NC=C1CC1=CC=CN=C1 ATAQPWJXJCSDKK-UHFFFAOYSA-N 0.000 description 1
- MGUJTLXGJTUBAR-UHFFFAOYSA-N 2-[2-[(3-fluoropyridin-2-yl)methylsulfanyl]ethylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound FC1=CC=CN=C1CSCCNC(NC1=O)=NC=C1CC1=CC=CN=C1 MGUJTLXGJTUBAR-UHFFFAOYSA-N 0.000 description 1
- CNUWFEXJECXEDK-UHFFFAOYSA-N 2-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethylamino]-5-(pyridazin-4-ylmethyl)-1h-pyrimidin-6-one Chemical compound N1C=NC(CSCCNC=2NC(=O)C(CC=3C=NN=CC=3)=CN=2)=C1C CNUWFEXJECXEDK-UHFFFAOYSA-N 0.000 description 1
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- SNCJKQCVQLVZPY-UHFFFAOYSA-N 2-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one;trihydrochloride Chemical compound Cl.Cl.Cl.N1C=NC(CSCCNC=2NC(=O)C(CC=3C=NC(C)=CC=3)=CN=2)=C1C SNCJKQCVQLVZPY-UHFFFAOYSA-N 0.000 description 1
- LKFQLYQRAVVCEJ-UHFFFAOYSA-N 2-[4-(3-bromopyridin-2-yl)butylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound BrC1=CC=CN=C1CCCCNC(NC1=O)=NC=C1CC1=CC=CN=C1 LKFQLYQRAVVCEJ-UHFFFAOYSA-N 0.000 description 1
- NPTIJBQFPCNGNO-UHFFFAOYSA-N 2-[4-(3-chloropyridin-2-yl)butylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound ClC1=CC=CN=C1CCCCNC(NC1=O)=NC=C1CC1=CC=CN=C1 NPTIJBQFPCNGNO-UHFFFAOYSA-N 0.000 description 1
- VZYKJBUUAXGMSD-UHFFFAOYSA-N 2-[4-(3-ethoxypyridin-2-yl)butylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound CCOC1=CC=CN=C1CCCCNC(NC1=O)=NC=C1CC1=CC=C(C)N=C1 VZYKJBUUAXGMSD-UHFFFAOYSA-N 0.000 description 1
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 1
- DEXXTYSZLNPKFH-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridazin-4-ylmethyl)-1h-pyrimidin-6-one Chemical compound N1C(SC)=NC(=O)C(CC=2C=NN=CC=2)=C1 DEXXTYSZLNPKFH-UHFFFAOYSA-N 0.000 description 1
- JAARZEYATGFNND-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyrimidin-4-ylmethyl)-1H-pyrimidin-6-one Chemical compound N1=CN=C(C=C1)CC=1C(NC(=NC=1)SC)=O JAARZEYATGFNND-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
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- OSJHHJFVPZUSRJ-UHFFFAOYSA-N 3-(2-chloro-5,6-dimethylpyridin-3-yl)prop-2-enoic acid Chemical compound CC1=CC(C=CC(O)=O)=C(Cl)N=C1C OSJHHJFVPZUSRJ-UHFFFAOYSA-N 0.000 description 1
- HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 1
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- SFGQJKFFQVMEQA-UHFFFAOYSA-N 4-(3-bromopyridin-2-yl)butan-1-amine Chemical compound NCCCCC1=NC=CC=C1Br SFGQJKFFQVMEQA-UHFFFAOYSA-N 0.000 description 1
- AISUFNDOCWBLFH-UHFFFAOYSA-N 4-(3-nitropyridin-2-yl)butanenitrile;hydrochloride Chemical compound Cl.[O-][N+](=O)C1=CC=CN=C1CCCC#N AISUFNDOCWBLFH-UHFFFAOYSA-N 0.000 description 1
- STIOUOHCWDHSJY-UHFFFAOYSA-N 4-pyridin-2-ylbutan-1-amine Chemical compound NCCCCC1=CC=CC=N1 STIOUOHCWDHSJY-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- WPSYKOQCIXXKSI-UHFFFAOYSA-N 5-(pyridin-3-ylmethyl)-2-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethylamino]-1H-pyrimidin-6-one trihydrobromide Chemical compound Br.Br.Br.N=1C=C(CC=2C=NC=CC=2)C(=O)NC=1NCCSCC1=NC=CS1 WPSYKOQCIXXKSI-UHFFFAOYSA-N 0.000 description 1
- RMAKEAAKXDXYMQ-UHFFFAOYSA-N 5-(pyridin-4-ylmethyl)-2-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethylamino]-1h-pyrimidin-6-one Chemical compound N=1C=C(CC=2C=CN=CC=2)C(=O)NC=1NCCSCC1=NC=CS1 RMAKEAAKXDXYMQ-UHFFFAOYSA-N 0.000 description 1
- VLJWPLQUEKZQPD-UHFFFAOYSA-N 5-[(2-methoxypyridin-4-yl)methyl]-2-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethylamino]-1h-pyrimidin-6-one Chemical compound C1=NC(OC)=CC(CC=2C(NC(NCCSCC=3SC=CN=3)=NC=2)=O)=C1 VLJWPLQUEKZQPD-UHFFFAOYSA-N 0.000 description 1
- AMGNSOJDRCRSKJ-UHFFFAOYSA-N 5-[(2-methoxypyridin-4-yl)methyl]-2-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethylamino]-1h-pyrimidin-6-one Chemical compound C1=NC(OC)=CC(CC=2C(NC(NCCSCC3=C(NC=N3)C)=NC=2)=O)=C1 AMGNSOJDRCRSKJ-UHFFFAOYSA-N 0.000 description 1
- LSXVIWRCROXVAH-UHFFFAOYSA-N 5-[(2-methoxypyridin-4-yl)methyl]-2-methylsulfanyl-1H-pyrimidin-6-one Chemical compound COC1=NC=CC(=C1)CC=1C(NC(=NC=1)SC)=O LSXVIWRCROXVAH-UHFFFAOYSA-N 0.000 description 1
- XQJIBQMPOYWNDZ-UHFFFAOYSA-N 5-[(5,6-dimethylpyridin-3-yl)methyl]-2-methylsulfanyl-1H-pyrimidin-6-one Chemical compound CC=1C=C(C=NC=1C)CC=1C(NC(=NC=1)SC)=O XQJIBQMPOYWNDZ-UHFFFAOYSA-N 0.000 description 1
- LAMWNDJMJLZNMI-UHFFFAOYSA-N 5-[(6-methoxypyridin-3-yl)methyl]-2-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethylamino]-1h-pyrimidin-6-one Chemical compound C1=NC(OC)=CC=C1CC(C(N1)=O)=CN=C1NCCSCC1=NC=CS1 LAMWNDJMJLZNMI-UHFFFAOYSA-N 0.000 description 1
- SHDSTKUGFWJBTJ-UHFFFAOYSA-N 5-[(6-methoxypyridin-3-yl)methyl]-2-methylsulfanyl-1H-pyrimidin-6-one Chemical compound COC1=CC=C(C=N1)CC=1C(NC(=NC=1)SC)=O SHDSTKUGFWJBTJ-UHFFFAOYSA-N 0.000 description 1
- VXAISYKQFCWPBO-UHFFFAOYSA-N 5-[(6-methylpyridin-3-yl)methyl]-2-(4-pyridin-2-ylbutylamino)-1h-pyrimidin-6-one Chemical compound C1=NC(C)=CC=C1CC(C(N1)=O)=CN=C1NCCCCC1=CC=CC=N1 VXAISYKQFCWPBO-UHFFFAOYSA-N 0.000 description 1
- AXNSHYDBYJWPHT-UHFFFAOYSA-N 5-[(6-methylpyridin-3-yl)methyl]-2-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethylamino]-1h-pyrimidin-6-one;trihydrochloride Chemical compound Cl.Cl.Cl.C1=NC(C)=CC=C1CC(C(N1)=O)=CN=C1NCCSCC1=NC=CS1 AXNSHYDBYJWPHT-UHFFFAOYSA-N 0.000 description 1
- DFPYAQAFVHRSAG-UHFFFAOYSA-N 6-methoxypyridine-3-carbonitrile Chemical compound COC1=CC=C(C#N)C=N1 DFPYAQAFVHRSAG-UHFFFAOYSA-N 0.000 description 1
- AHISYUZBWDSPQL-UHFFFAOYSA-N 6-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=CC(C=O)=N1 AHISYUZBWDSPQL-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- IIRNTAUHCUFDSU-UHFFFAOYSA-N CC1=CC=C(CC2=COC(NCCCCC3=NC=CC=C3OC)=CC2=N)C=N1.Cl.Cl.Cl Chemical compound CC1=CC=C(CC2=COC(NCCCCC3=NC=CC=C3OC)=CC2=N)C=N1.Cl.Cl.Cl IIRNTAUHCUFDSU-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- GRESEHVSJAAWFF-UHFFFAOYSA-N Cl.Cl.Cl.CC1=C(N=CN1)CSCCNC1=NC=C(C(N1)=O)CC=1C=NC(=CC1)OC Chemical compound Cl.Cl.Cl.CC1=C(N=CN1)CSCCNC1=NC=C(C(N1)=O)CC=1C=NC(=CC1)OC GRESEHVSJAAWFF-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- CRDJNKFVVRGPJM-UHFFFAOYSA-N N1=NC=C(C=C1)C(C(=O)O)=C Chemical compound N1=NC=C(C=C1)C(C(=O)O)=C CRDJNKFVVRGPJM-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102100037483 POU domain, class 6, transcription factor 1 Human genes 0.000 description 1
- 101710196406 POU domain, class 6, transcription factor 1 Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- YJJLOESDBPRZIP-UHFFFAOYSA-N diethyl 2-(2-cyanoethyl)propanedioate Chemical compound CCOC(=O)C(CCC#N)C(=O)OCC YJJLOESDBPRZIP-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- FCISHUHNFYJJDU-UHFFFAOYSA-N ethyl 2-cyanobutanoate Chemical compound CCOC(=O)C(CC)C#N FCISHUHNFYJJDU-UHFFFAOYSA-N 0.000 description 1
- MHHUXKYMQGCHOW-UHFFFAOYSA-N ethyl 2-formyl-3-(6-methoxypyridin-3-yl)propanoate Chemical compound CCOC(=O)C(C=O)CC1=CC=C(OC)N=C1 MHHUXKYMQGCHOW-UHFFFAOYSA-N 0.000 description 1
- ANSAXZVCVFZRFF-UHFFFAOYSA-N ethyl 2-thiophen-2-ylpropanoate Chemical compound CCOC(=O)C(C)C1=CC=CS1 ANSAXZVCVFZRFF-UHFFFAOYSA-N 0.000 description 1
- FDUJSLFRGSYDGZ-UHFFFAOYSA-N ethyl 3-(1,3-thiazol-2-yl)propanoate Chemical compound CCOC(=O)CCC1=NC=CS1 FDUJSLFRGSYDGZ-UHFFFAOYSA-N 0.000 description 1
- HMKDTADHIZUAIK-UHFFFAOYSA-N ethyl 3-(2-chloro-5,6-dimethylpyridin-3-yl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC(C)=C(C)N=C1Cl HMKDTADHIZUAIK-UHFFFAOYSA-N 0.000 description 1
- IQXXDFIZZHXWBM-UHFFFAOYSA-N ethyl 3-(6-methoxypyridin-3-yl)prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC=C(OC)N=C1 IQXXDFIZZHXWBM-UHFFFAOYSA-N 0.000 description 1
- QYWJJYWOBGZKHP-UHFFFAOYSA-N ethyl 3-(6-methoxypyridin-3-yl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(OC)N=C1 QYWJJYWOBGZKHP-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- ZJXZSIYSNXKHEA-UHFFFAOYSA-N ethyl dihydrogen phosphate Chemical compound CCOP(O)(O)=O ZJXZSIYSNXKHEA-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB5300175 | 1975-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS203995B2 true CS203995B2 (en) | 1981-03-31 |
Family
ID=10466233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS768760A CS203995B2 (en) | 1975-12-29 | 1976-12-29 | Method of producing heterocyclic compounds |
Country Status (37)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ186511A (en) | 1977-03-19 | 1980-11-14 | Smith Kline French Lab | 3-substituted alkylamino-6-substituted alkyl-1,2,4-triazin-5-ones and pharmaceutical compositions 3-substituted thio-1,2,4-triazin-5-ones |
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
| US4539207A (en) * | 1978-02-13 | 1985-09-03 | Smith Kline & French Laboratories Limited | Pyrimidine compounds |
| IN151188B (enrdf_load_stackoverflow) * | 1978-02-13 | 1983-03-05 | Smith Kline French Lab | |
| IL57005A (en) * | 1978-04-11 | 1983-11-30 | Smith Kline French Lab | Process for the preparation of 2-amino pyrimid-4-one derivatives and novel 2-nitroaminopyrimid-4-ones as intermediates therefor |
| ZA792607B (en) * | 1978-05-30 | 1980-07-30 | Smith Kline French Lab | Nitro compounds |
| ZA793392B (en) * | 1978-07-15 | 1980-08-27 | Smith Kline French Lab | Isoureas and isothioureas |
| US4374836A (en) | 1978-10-16 | 1983-02-22 | Imperial Chemical Industries Ltd. | Antisecretory heterocyclic derivatives, process for their manufacture and pharmaceutical compositions containing them |
| US4309435A (en) | 1978-10-16 | 1982-01-05 | Imperial Chemical Industries Ltd. | Antisecretory guanidine derivatives and pharmaceutical compositions containing them |
| US4496567A (en) * | 1978-11-13 | 1985-01-29 | Smith Kline & French Laboratories Limited | Phenyl alkylaminopyrimidones |
| US4521418A (en) * | 1979-02-21 | 1985-06-04 | Smith Kline & French Laboratories Limited | Guanidinothiazolyl derivatives |
| US4255428A (en) | 1979-03-24 | 1981-03-10 | Smith Kline & French Laboratories Limited | 5-(Hydroxypyridylalkyl)-4-pyrimidones |
| JPS55133379A (en) * | 1979-04-05 | 1980-10-17 | Smith Kline French Lab | Pyrimidone compound |
| EP0017680B1 (en) * | 1979-04-11 | 1982-04-21 | Smith Kline & French Laboratories Limited | Pyrimidone derivatives, process for preparing them and pharmaceutical compositions containing them |
| JPS55145683A (en) * | 1979-04-26 | 1980-11-13 | Smith Kline French Lab | Pyrimidone derivative |
| CA1155842A (en) * | 1980-03-29 | 1983-10-25 | Thomas H. Brown | Compounds |
| ZW21281A1 (en) * | 1980-10-01 | 1981-11-18 | Smith Kline French Lab | Amine derivatives |
| IE53068B1 (en) * | 1981-06-15 | 1988-05-25 | Merck & Co Inc | Diamino isothiazole-1-oxides and -1,1-dioxides as gastic secretion inhibitors |
| PT75074B (en) * | 1981-06-27 | 1986-02-26 | Smith Kline French Lab | Process for preparing certain pyrimidone derivatives and compositions containing them |
| US6417366B2 (en) * | 1999-06-24 | 2002-07-09 | Abbott Laboratories | Preparation of quinoline-substituted carbonate and carbamate derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1419994A (en) * | 1973-05-03 | 1976-01-07 | Smith Kline French Lab | Heterocyclicalkylaminotheterocyclic compounds methods for their preparation and compositions comprising them |
| IN146736B (enrdf_load_stackoverflow) * | 1975-10-02 | 1979-08-25 | Smith Kline French Lab |
-
1976
- 1976-11-22 MW MW50/76A patent/MW5076A1/xx unknown
- 1976-11-29 NZ NZ182759A patent/NZ182759A/xx unknown
- 1976-12-02 ZA ZA767198A patent/ZA767198B/xx unknown
- 1976-12-02 IL IL51040A patent/IL51040A/xx unknown
- 1976-12-08 CA CA267,385A patent/CA1073458A/en not_active Expired
- 1976-12-09 IT IT30235/76A patent/IT1124740B/it active
- 1976-12-10 PT PT65949A patent/PT65949B/pt unknown
- 1976-12-17 PH PH19265A patent/PH14723A/en unknown
- 1976-12-17 ZM ZM143/76A patent/ZM14376A1/xx unknown
- 1976-12-21 FI FI763664A patent/FI62668C/fi not_active IP Right Cessation
- 1976-12-22 DE DE19762658267 patent/DE2658267A1/de not_active Ceased
- 1976-12-22 YU YU03116/76A patent/YU311676A/xx unknown
- 1976-12-22 IE IE2814/76A patent/IE45082B1/en unknown
- 1976-12-22 GR GR52462A patent/GR62441B/el unknown
- 1976-12-23 JP JP15611076A patent/JPS5283388A/ja active Granted
- 1976-12-23 BE BE173597A patent/BE849810A/xx not_active IP Right Cessation
- 1976-12-23 CH CH1627876A patent/CH631981A5/de not_active IP Right Cessation
- 1976-12-23 AT AT960876A patent/AT360024B/de not_active IP Right Cessation
- 1976-12-27 RO RO7688851A patent/RO72475A/ro unknown
- 1976-12-28 NO NO764370A patent/NO146396C/no unknown
- 1976-12-28 PL PL1976194772A patent/PL104376B1/pl unknown
- 1976-12-28 HU HU76SI1556A patent/HU175171B/hu unknown
- 1976-12-28 BG BG035033A patent/BG29722A3/xx unknown
- 1976-12-28 EG EG803/76A patent/EG12439A/xx active
- 1976-12-28 SE SE7614620A patent/SE431544B/xx not_active IP Right Cessation
- 1976-12-28 LU LU76481A patent/LU76481A1/xx unknown
- 1976-12-29 DD DD7600196703A patent/DD128588A5/xx unknown
- 1976-12-29 OA OA56028A patent/OA05526A/xx unknown
- 1976-12-29 DK DK587076A patent/DK587076A/da not_active Application Discontinuation
- 1976-12-29 NL NL7614538A patent/NL7614538A/xx not_active Application Discontinuation
- 1976-12-29 FR FR7639465A patent/FR2336935A1/fr active Granted
- 1976-12-29 CS CS768760A patent/CS203995B2/cs unknown
- 1976-12-29 ES ES454656A patent/ES454656A1/es not_active Expired
- 1976-12-29 AR AR266049A patent/AR222290A1/es active
- 1976-12-29 SU SU762434655A patent/SU791235A3/ru active
- 1976-12-30 AU AU20976/76A patent/AU508123B2/en not_active Expired
-
1977
- 1977-01-03 MX MX775273U patent/MX5119E/es unknown
-
1979
- 1979-01-05 IT IT7919107A patent/IT7919107A0/it unknown
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