CS215055B2 - Method of making the substituted 2-aminopyrazines - Google Patents
Method of making the substituted 2-aminopyrazines Download PDFInfo
- Publication number
- CS215055B2 CS215055B2 CS802293A CS229380A CS215055B2 CS 215055 B2 CS215055 B2 CS 215055B2 CS 802293 A CS802293 A CS 802293A CS 229380 A CS229380 A CS 229380A CS 215055 B2 CS215055 B2 CS 215055B2
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- Czechoslovakia
- Prior art keywords
- substituted
- reaction
- mol
- acid
- mixture
- Prior art date
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- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical class NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims abstract description 33
- -1 hydroxyimino-substituted aminoacetonitrile Chemical class 0.000 claims abstract description 30
- 238000002360 preparation method Methods 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 101100515516 Arabidopsis thaliana XI-H gene Proteins 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 33
- 239000002253 acid Substances 0.000 abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 20
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 abstract description 14
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 abstract description 14
- 229910000147 aluminium phosphate Inorganic materials 0.000 abstract description 5
- 239000001257 hydrogen Substances 0.000 abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 239000000047 product Substances 0.000 description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000000243 solution Substances 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 229910052799 carbon Inorganic materials 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 238000007363 ring formation reaction Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000004157 Nitrosyl chloride Substances 0.000 description 11
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 11
- 150000008361 aminoacetonitriles Chemical class 0.000 description 11
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 11
- 235000019392 nitrosyl chloride Nutrition 0.000 description 11
- 229910052794 bromium Chemical group 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000011230 binding agent Substances 0.000 description 8
- 239000002274 desiccant Substances 0.000 description 8
- 150000003440 styrenes Chemical class 0.000 description 8
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 235000011007 phosphoric acid Nutrition 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 239000000538 analytical sample Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- SMYHFDLFOKKDOO-UHFFFAOYSA-N 1-(2-bromophenyl)propan-1-ol Chemical compound CCC(O)C1=CC=CC=C1Br SMYHFDLFOKKDOO-UHFFFAOYSA-N 0.000 description 3
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NTTBDWAXCRRVJY-UHFFFAOYSA-N 1-(4-ethylphenyl)propan-1-ol Chemical compound CCC(O)C1=CC=C(CC)C=C1 NTTBDWAXCRRVJY-UHFFFAOYSA-N 0.000 description 2
- VGQRIILEZYZAOE-UHFFFAOYSA-N 1-(4-ethylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(CC)C=C1 VGQRIILEZYZAOE-UHFFFAOYSA-N 0.000 description 2
- IPDBNWOEFLIODE-UHFFFAOYSA-N 1-bromo-2-prop-1-enylbenzene Chemical compound CC=CC1=CC=CC=C1Br IPDBNWOEFLIODE-UHFFFAOYSA-N 0.000 description 2
- MKJOTWMWLNTTJM-UHFFFAOYSA-N 1-ethyl-4-prop-1-enylbenzene Chemical group CCC1=CC=C(C=CC)C=C1 MKJOTWMWLNTTJM-UHFFFAOYSA-N 0.000 description 2
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- SJYCYRJOUJAQFB-UHFFFAOYSA-N 5-(4-bromophenyl)-6-methylpyrazin-2-amine Chemical compound CC1=NC(N)=CN=C1C1=CC=C(Br)C=C1 SJYCYRJOUJAQFB-UHFFFAOYSA-N 0.000 description 2
- NFFWTXKHMBVZFK-UHFFFAOYSA-N 6-methyl-5-phenylpyrazin-2-amine Chemical compound CC1=NC(N)=CN=C1C1=CC=CC=C1 NFFWTXKHMBVZFK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- QROGIFZRVHSFLM-QHHAFSJGSA-N [(e)-prop-1-enyl]benzene Chemical compound C\C=C\C1=CC=CC=C1 QROGIFZRVHSFLM-QHHAFSJGSA-N 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000003541 multi-stage reaction Methods 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical class C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- DBASWHONNARUPG-UHFFFAOYSA-N 1,2-dichloro-4-prop-1-enylbenzene Chemical compound CC=CC1=CC=C(Cl)C(Cl)=C1 DBASWHONNARUPG-UHFFFAOYSA-N 0.000 description 1
- KZNLLGVHMGYUAX-UHFFFAOYSA-N 1-bromo-4-prop-1-enylbenzene Chemical compound CC=CC1=CC=C(Br)C=C1 KZNLLGVHMGYUAX-UHFFFAOYSA-N 0.000 description 1
- KFPLPFVPPOJDFF-UHFFFAOYSA-N 1-chloro-1-phenylpropan-2-one Chemical compound CC(=O)C(Cl)C1=CC=CC=C1 KFPLPFVPPOJDFF-UHFFFAOYSA-N 0.000 description 1
- RMTFLXQMWNPEMG-UHFFFAOYSA-N 1-ethyl-2-prop-1-enylbenzene Chemical compound CCC1=CC=CC=C1C=CC RMTFLXQMWNPEMG-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- CQXMBSOTZBZEPY-UHFFFAOYSA-N 2-[(2-hydroxyimino-1-phenylpropyl)amino]acetonitrile Chemical compound N#CCNC(C(=NO)C)C1=CC=CC=C1 CQXMBSOTZBZEPY-UHFFFAOYSA-N 0.000 description 1
- QHBJNPWYPLXNSI-UHFFFAOYSA-N 2-[[1-(4-ethylphenyl)-2-hydroxyiminopropyl]amino]acetonitrile Chemical compound CCC1=CC=C(C(NCC#N)C(C)=NO)C=C1 QHBJNPWYPLXNSI-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- RIKLWNXUCIOIPI-UHFFFAOYSA-N 5-(3-bromophenyl)-6-methylpyrazin-2-amine Chemical compound CC1=NC(N)=CN=C1C1=CC=CC(Br)=C1 RIKLWNXUCIOIPI-UHFFFAOYSA-N 0.000 description 1
- QYCWZGDAYYKQTL-UHFFFAOYSA-N 5-(4-bromophenyl)-6-ethylpyrazin-2-amine Chemical compound CCC1=NC(N)=CN=C1C1=CC=C(Br)C=C1 QYCWZGDAYYKQTL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- YKGPLGQFEQISRN-UHFFFAOYSA-N CCC(=NO)C(Cl)C1=CC=C(Br)C=C1 Chemical compound CCC(=NO)C(Cl)C1=CC=C(Br)C=C1 YKGPLGQFEQISRN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 101000933374 Gallus gallus Brain-specific homeobox/POU domain protein 3 Proteins 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- XHDBQDSIMYOXBU-UHFFFAOYSA-N N-[1-chloro-1-(2,4-dimethylphenyl)propan-2-ylidene]hydroxylamine Chemical compound ON=C(C)C(Cl)C1=CC=C(C)C=C1C XHDBQDSIMYOXBU-UHFFFAOYSA-N 0.000 description 1
- HEHVCMHKHXZXLJ-UHFFFAOYSA-N N-[1-chloro-1-(4-chlorophenyl)propan-2-ylidene]hydroxylamine Chemical compound ON=C(C)C(Cl)C1=CC=C(Cl)C=C1 HEHVCMHKHXZXLJ-UHFFFAOYSA-N 0.000 description 1
- OCAAIVJYAVLKHY-UHFFFAOYSA-N ON=C(C)C(Cl)C1=CC=C(Br)C=C1 Chemical compound ON=C(C)C(Cl)C1=CC=C(Br)C=C1 OCAAIVJYAVLKHY-UHFFFAOYSA-N 0.000 description 1
- MIGIDHDRZQLPBH-UHFFFAOYSA-N ON=C(C)C(Cl)C1=CC=CC(Br)=C1 Chemical compound ON=C(C)C(Cl)C1=CC=CC(Br)=C1 MIGIDHDRZQLPBH-UHFFFAOYSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- KFCUPNHUPHDVJC-UHFFFAOYSA-N bromine azide Chemical compound BrN=[N+]=[N-] KFCUPNHUPHDVJC-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- HSSFHZJIMRUXDM-UHFFFAOYSA-N hydroxy(oxo)azanium chloride Chemical compound Cl.[O-][NH+]=O HSSFHZJIMRUXDM-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- DDCYYCUMAFYDDU-UHFFFAOYSA-N methyl thiohypochlorite Chemical compound CSCl DDCYYCUMAFYDDU-UHFFFAOYSA-N 0.000 description 1
- JIMRVZGQHAUYPJ-UHFFFAOYSA-N n-(1-chloro-1-phenylpropan-2-ylidene)hydroxylamine Chemical compound ON=C(C)C(Cl)C1=CC=CC=C1 JIMRVZGQHAUYPJ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- VQTGUFBGYOIUFS-UHFFFAOYSA-N nitrosylsulfuric acid Chemical compound OS(=O)(=O)ON=O VQTGUFBGYOIUFS-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
- C07C29/40—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing carbon-to-metal bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
- C07C33/20—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part monocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12C—BEER; PREPARATION OF BEER BY FERMENTATION; PREPARATION OF MALT FOR MAKING BEER; PREPARATION OF HOPS FOR MAKING BEER
- C12C11/00—Fermentation processes for beer
- C12C11/02—Pitching yeast
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Food Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Mycology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/027,630 US4211870A (en) | 1979-04-06 | 1979-04-06 | Preparation of substituted 2-aminopyrazines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS215055B2 true CS215055B2 (en) | 1982-07-30 |
Family
ID=21838837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS802293A CS215055B2 (en) | 1979-04-06 | 1980-04-02 | Method of making the substituted 2-aminopyrazines |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4211870A (en]) |
| EP (1) | EP0018144A1 (en]) |
| JP (1) | JPS55141473A (en]) |
| KR (1) | KR830002731A (en]) |
| AU (1) | AU5710280A (en]) |
| BE (1) | BE882608A (en]) |
| BR (1) | BR8002079A (en]) |
| CA (1) | CA1157860A (en]) |
| CS (1) | CS215055B2 (en]) |
| DD (1) | DD150057A5 (en]) |
| DK (1) | DK144280A (en]) |
| ES (1) | ES8105303A1 (en]) |
| FI (1) | FI801056A7 (en]) |
| FR (1) | FR2453159A1 (en]) |
| GB (1) | GB2046751A (en]) |
| GR (1) | GR68096B (en]) |
| IL (1) | IL59761A0 (en]) |
| IT (1) | IT1147345B (en]) |
| LU (1) | LU82342A1 (en]) |
| NZ (1) | NZ193345A (en]) |
| PL (1) | PL223264A1 (en]) |
| PT (1) | PT71056A (en]) |
| RO (1) | RO79384A (en]) |
| SU (1) | SU932989A3 (en]) |
| ZA (1) | ZA802005B (en]) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2209465C (en) * | 1996-07-11 | 2008-04-29 | Lonza Ag | Process for preparing 3-alkoxy-5-alkylpyrazin-2-amines |
| EE200200453A (et) * | 2000-02-16 | 2003-12-15 | Neurogen Corporation | Asendatud arüülpürasiinid |
| CA2496197A1 (en) * | 2002-08-20 | 2004-03-04 | Neurogen Corporation | 5-substituted-2-arylpyrazines as modulators of crf receptors |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE794329A (fr) * | 1972-01-20 | 1973-07-19 | Pechiney Ugine Kuhlmann | Derives d'aza-2 butadienes-1,3 et procede pour leur preparation |
| EG11837A (en) * | 1974-09-19 | 1977-12-31 | Lilly Co Eli | Novel 1-(substituted benzoyl)-3-(substituted pyrazinyl ureas used as insecticides |
| US4160834A (en) * | 1977-03-09 | 1979-07-10 | Eli Lilly And Company | 1-(Substituted benzoyl)-3-(substituted pyrazinyl)ureas |
-
1979
- 1979-04-06 US US06/027,630 patent/US4211870A/en not_active Expired - Lifetime
-
1980
- 1980-04-02 PT PT71056A patent/PT71056A/pt unknown
- 1980-04-02 CA CA000349061A patent/CA1157860A/en not_active Expired
- 1980-04-02 CS CS802293A patent/CS215055B2/cs unknown
- 1980-04-02 BR BR8002079A patent/BR8002079A/pt unknown
- 1980-04-02 AU AU57102/80A patent/AU5710280A/en not_active Abandoned
- 1980-04-02 DK DK144280A patent/DK144280A/da unknown
- 1980-04-02 FI FI801056A patent/FI801056A7/fi not_active Application Discontinuation
- 1980-04-02 NZ NZ193345A patent/NZ193345A/xx unknown
- 1980-04-02 FR FR8007457A patent/FR2453159A1/fr not_active Withdrawn
- 1980-04-02 ES ES490287A patent/ES8105303A1/es not_active Expired
- 1980-04-02 GR GR61609A patent/GR68096B/el unknown
- 1980-04-03 IL IL59761A patent/IL59761A0/xx unknown
- 1980-04-03 DD DD80220207A patent/DD150057A5/de unknown
- 1980-04-03 GB GB8011363A patent/GB2046751A/en not_active Withdrawn
- 1980-04-03 BE BE1/9771A patent/BE882608A/fr unknown
- 1980-04-03 ZA ZA00802005A patent/ZA802005B/xx unknown
- 1980-04-03 EP EP80301085A patent/EP0018144A1/en not_active Ceased
- 1980-04-04 RO RO80100722A patent/RO79384A/ro unknown
- 1980-04-04 PL PL22326480A patent/PL223264A1/xx unknown
- 1980-04-04 IT IT21231/80A patent/IT1147345B/it active
- 1980-04-04 KR KR1019800001429A patent/KR830002731A/ko not_active Abandoned
- 1980-04-04 LU LU82342A patent/LU82342A1/fr unknown
- 1980-04-04 SU SU802902455A patent/SU932989A3/ru active
- 1980-04-05 JP JP4511480A patent/JPS55141473A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PL223264A1 (en]) | 1981-01-30 |
| GR68096B (en]) | 1981-10-30 |
| IT1147345B (it) | 1986-11-19 |
| JPS55141473A (en) | 1980-11-05 |
| LU82342A1 (fr) | 1980-07-02 |
| ES490287A0 (es) | 1981-05-16 |
| US4211870A (en) | 1980-07-08 |
| NZ193345A (en) | 1982-11-23 |
| IT8021231A0 (it) | 1980-04-04 |
| ZA802005B (en) | 1981-11-25 |
| DK144280A (da) | 1980-10-07 |
| FI801056A7 (fi) | 1980-10-07 |
| SU932989A3 (ru) | 1982-05-30 |
| BE882608A (fr) | 1980-10-03 |
| CA1157860A (en) | 1983-11-29 |
| PT71056A (en) | 1980-05-01 |
| RO79384A (ro) | 1982-06-25 |
| FR2453159A1 (fr) | 1980-10-31 |
| IL59761A0 (en) | 1980-06-30 |
| GB2046751A (en) | 1980-11-19 |
| ES8105303A1 (es) | 1981-05-16 |
| KR830002731A (ko) | 1983-05-30 |
| EP0018144A1 (en) | 1980-10-29 |
| AU5710280A (en) | 1980-10-09 |
| DD150057A5 (de) | 1981-08-12 |
| BR8002079A (pt) | 1980-11-25 |
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