CS241025B2 - Method of fussed pyrimidine-4-ons' dihalogenated derivatives production - Google Patents
Method of fussed pyrimidine-4-ons' dihalogenated derivatives production Download PDFInfo
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- CS241025B2 CS241025B2 CS803258A CS325880A CS241025B2 CS 241025 B2 CS241025 B2 CS 241025B2 CS 803258 A CS803258 A CS 803258A CS 325880 A CS325880 A CS 325880A CS 241025 B2 CS241025 B2 CS 241025B2
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- Czechoslovakia
- Prior art keywords
- formula
- compound
- hydrogen
- compounds
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 27
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 13
- -1 cyano, phenyl Chemical group 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 230000002140 halogenating effect Effects 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000007858 starting material Substances 0.000 claims abstract description 7
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
- 230000031709 bromination Effects 0.000 claims description 3
- 238000005893 bromination reaction Methods 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 238000006114 decarboxylation reaction Methods 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 1
- 150000003949 imides Chemical class 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 3
- 125000004185 ester group Chemical group 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000001766 physiological effect Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 229960001701 chloroform Drugs 0.000 description 22
- 239000000243 solution Substances 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 7
- CSOYDALHEQEMAK-UHFFFAOYSA-N 2h-pyrimidine-1-carboxylic acid Chemical compound OC(=O)N1CN=CC=C1 CSOYDALHEQEMAK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 230000003266 anti-allergic effect Effects 0.000 description 4
- 230000001088 anti-asthma Effects 0.000 description 4
- 239000000924 antiasthmatic agent Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- KOXNRJHZWXSKMF-UHFFFAOYSA-N 6-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCCC2=N1 KOXNRJHZWXSKMF-UHFFFAOYSA-N 0.000 description 3
- HCJOGZBBWGQKGC-UHFFFAOYSA-N 6-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(=O)N2C(C)CCCC2=N1 HCJOGZBBWGQKGC-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000002930 anti-sclerotic effect Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- SEISMQVOJUJKGE-UHFFFAOYSA-M ethyl 1,6-dimethyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-1-ium-3-carboxylate;methyl sulfate Chemical compound COS([O-])(=O)=O.C1CCC(C)N2C(=O)C(C(=O)OCC)=C[N+](C)=C21 SEISMQVOJUJKGE-UHFFFAOYSA-M 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- WJUKOGPNGRUXMG-UHFFFAOYSA-N 1,2-dibromo-1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)(Br)C(Cl)(Cl)Br WJUKOGPNGRUXMG-UHFFFAOYSA-N 0.000 description 1
- QLAJNZSPVITUCQ-UHFFFAOYSA-N 1,3,2-dioxathietane 2,2-dioxide Chemical compound O=S1(=O)OCO1 QLAJNZSPVITUCQ-UHFFFAOYSA-N 0.000 description 1
- FVZLXIARAAOVCZ-UHFFFAOYSA-N 1h-azepine-3-carboxylic acid Chemical compound OC(=O)C1=CNC=CC=C1 FVZLXIARAAOVCZ-UHFFFAOYSA-N 0.000 description 1
- WHTZQYDVDPHTAM-UHFFFAOYSA-N 2,2,2-tribromo-1-phenylethanone Chemical compound BrC(Br)(Br)C(=O)C1=CC=CC=C1 WHTZQYDVDPHTAM-UHFFFAOYSA-N 0.000 description 1
- TZJKBFRUMZLUME-UHFFFAOYSA-N 2,2-dibromo-1,4-dioxane Chemical compound BrC1(Br)COCCO1 TZJKBFRUMZLUME-UHFFFAOYSA-N 0.000 description 1
- QLENPRKQIFCBST-UHFFFAOYSA-N 3,6-dimethyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(C)C(=O)N2C(C)CCCC2=N1 QLENPRKQIFCBST-UHFFFAOYSA-N 0.000 description 1
- GRDANFRPPNRFBV-UHFFFAOYSA-N 6-methyl-2-phenyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound C1(=CC=CC=C1)C=1N=C2N(C(C=1)=O)C(CCC2)C GRDANFRPPNRFBV-UHFFFAOYSA-N 0.000 description 1
- HNTWDRHOLWKXFX-UHFFFAOYSA-N 9,9-dibromo-3,6-dimethyl-7,8-dihydro-6h-pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(C)C(=O)N2C(C)CCC(Br)(Br)C2=N1 HNTWDRHOLWKXFX-UHFFFAOYSA-N 0.000 description 1
- JSONPMDHAHNDDX-UHFFFAOYSA-N 9,9-dibromo-6-methyl-3-phenyl-7,8-dihydro-6h-pyrido[1,2-a]pyrimidin-4-one Chemical compound O=C1N2C(C)CCC(Br)(Br)C2=NC=C1C1=CC=CC=C1 JSONPMDHAHNDDX-UHFFFAOYSA-N 0.000 description 1
- YWLVFQUVWLTLJA-UHFFFAOYSA-N 9,9-dibromo-6-methyl-4-oxo-7,8-dihydro-6h-pyrido[1,2-a]pyrimidine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(=O)N2C(C)CCC(Br)(Br)C2=N1 YWLVFQUVWLTLJA-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- NZIUIJUSQQFSFK-UHFFFAOYSA-N Br.Cl.Cl.Cl.Cl Chemical compound Br.Cl.Cl.Cl.Cl NZIUIJUSQQFSFK-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DTUNKKWUXHBUHO-UHFFFAOYSA-N [Br].Br.C1=CC=NC=C1 Chemical compound [Br].Br.C1=CC=NC=C1 DTUNKKWUXHBUHO-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ILYWMFFSYODXAH-UHFFFAOYSA-N ethyl 10,10-dibromo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]azepine-3-carboxylate Chemical compound BrC1(C=2N(CCCC1)CC(=CC2)C(=O)OCC)Br ILYWMFFSYODXAH-UHFFFAOYSA-N 0.000 description 1
- WXOQPVPCAAVXOV-UHFFFAOYSA-N ethyl 4-oxo-7,8-dihydro-6h-pyrrolo[1,2-a]pyrimidine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=CN=C2CCCN21 WXOQPVPCAAVXOV-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 101150115538 nero gene Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- IUBKMGVNAYWGSL-UHFFFAOYSA-N pyrimidin-2-yl hydrogen carbonate Chemical compound OC(=O)OC1=NC=CC=N1 IUBKMGVNAYWGSL-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960000416 rimazolium Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- NBNBICNWNFQDDD-UHFFFAOYSA-N sulfuryl dibromide Chemical compound BrS(Br)(=O)=O NBNBICNWNFQDDD-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-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
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B62/00—Reactive dyes, i.e. dyes which form covalent bonds with the substrates or which polymerise with themselves
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (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)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU79CI1932A HU179443B (en) | 1979-05-11 | 1979-05-11 | Process for producing substituted geminal dihalogeno-derivatives of pyrido-square bracket-1,2-a-square closed-pyrimidines,pyrrolo-square bracket-1,2-a-square bracket closed-pyrimidines and pyrimido-square bracket-1,2,-a-square bracket closed-asepines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS325880A2 CS325880A2 (en) | 1985-06-13 |
| CS241025B2 true CS241025B2 (en) | 1986-03-13 |
Family
ID=10994747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS803258A CS241025B2 (en) | 1979-05-11 | 1980-05-08 | Method of fussed pyrimidine-4-ons' dihalogenated derivatives production |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPS5615286A (en]) |
| AT (1) | AT377261B (en]) |
| BE (1) | BE883217A (en]) |
| CA (1) | CA1141379A (en]) |
| CH (1) | CH646971A5 (en]) |
| CS (1) | CS241025B2 (en]) |
| DD (1) | DD150605A5 (en]) |
| DE (1) | DE3017564A1 (en]) |
| DK (1) | DK204680A (en]) |
| ES (1) | ES8102570A1 (en]) |
| FI (1) | FI68825C (en]) |
| FR (1) | FR2456101A1 (en]) |
| GB (1) | GB2051048B (en]) |
| GR (1) | GR68518B (en]) |
| HU (1) | HU179443B (en]) |
| IL (1) | IL59967A (en]) |
| IT (1) | IT1133085B (en]) |
| LU (1) | LU82437A1 (en]) |
| NL (1) | NL8002678A (en]) |
| NO (1) | NO152607C (en]) |
| PL (1) | PL124035B1 (en]) |
| PT (1) | PT71213A (en]) |
| SE (1) | SE441747B (en]) |
| SU (1) | SU1151210A3 (en]) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU178453B (en) * | 1979-05-11 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing 9-hydrazino-4-oxo-6,7,8,9-tetrahydro-4h-p-pyrido-square bracket-1,2-a-square bracket closed-pyrimidine derivatives |
| US4395549A (en) | 1981-10-02 | 1983-07-26 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | 6-Hydrazono-pyrido[2,1-b] quinazoline-11 ones |
| ES8501397A1 (es) * | 1982-08-05 | 1984-11-16 | Erba Farmitalia | "procedimiento para preparar derivados de quinazolina" |
| US5158952A (en) * | 1988-11-07 | 1992-10-27 | Janssen Pharmaceutica N.V. | 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use |
| UA72189C2 (uk) | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT299212B (de) * | 1966-11-02 | 1972-06-12 | Chinoin Gyogyszer Es Vegyeszet | Verfahren zur Herstellung von neuen Homopyrimidazol-Derivaten sowie von deren Salzen |
| HU178496B (en) * | 1977-12-29 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing 6,7,8,9-tetrahydro-4h-pyrido/1,2-a/pyrimidine derivatives with antiallergic activity |
-
1979
- 1979-05-11 HU HU79CI1932A patent/HU179443B/hu unknown
-
1980
- 1980-05-01 IL IL59967A patent/IL59967A/xx unknown
- 1980-05-03 GR GR61852A patent/GR68518B/el unknown
- 1980-05-08 CS CS803258A patent/CS241025B2/cs unknown
- 1980-05-08 SU SU802920002A patent/SU1151210A3/ru active
- 1980-05-08 DE DE19803017564 patent/DE3017564A1/de not_active Withdrawn
- 1980-05-08 SE SE8003479A patent/SE441747B/sv not_active IP Right Cessation
- 1980-05-09 NL NL8002678A patent/NL8002678A/nl not_active Application Discontinuation
- 1980-05-09 NO NO801378A patent/NO152607C/no unknown
- 1980-05-09 JP JP6161680A patent/JPS5615286A/ja active Pending
- 1980-05-09 DK DK204680A patent/DK204680A/da not_active Application Discontinuation
- 1980-05-09 AT AT0247580A patent/AT377261B/de not_active IP Right Cessation
- 1980-05-09 CA CA000351662A patent/CA1141379A/en not_active Expired
- 1980-05-09 CH CH366380A patent/CH646971A5/de not_active IP Right Cessation
- 1980-05-09 FR FR8010481A patent/FR2456101A1/fr active Granted
- 1980-05-09 IT IT67719/80A patent/IT1133085B/it active
- 1980-05-09 BE BE0/200550A patent/BE883217A/fr not_active IP Right Cessation
- 1980-05-09 GB GB8015469A patent/GB2051048B/en not_active Expired
- 1980-05-09 FI FI801512A patent/FI68825C/fi not_active IP Right Cessation
- 1980-05-09 LU LU82437A patent/LU82437A1/fr unknown
- 1980-05-09 PT PT71213A patent/PT71213A/pt unknown
- 1980-05-10 PL PL1980224163A patent/PL124035B1/pl unknown
- 1980-05-12 ES ES491896A patent/ES8102570A1/es not_active Expired
- 1980-05-12 DD DD80221053A patent/DD150605A5/de unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IT8067719A0 (it) | 1980-05-09 |
| ATA247580A (de) | 1984-07-15 |
| PL224163A1 (en]) | 1981-02-13 |
| IL59967A0 (en) | 1980-07-31 |
| ES491896A0 (es) | 1981-02-16 |
| NO152607C (no) | 1985-10-23 |
| HU179443B (en) | 1982-10-28 |
| NO801378L (no) | 1980-11-12 |
| CH646971A5 (de) | 1984-12-28 |
| SE8003479L (sv) | 1980-11-12 |
| SE441747B (sv) | 1985-11-04 |
| DK204680A (da) | 1980-11-12 |
| FI801512A7 (fi) | 1980-11-12 |
| BE883217A (fr) | 1980-09-01 |
| FI68825C (fi) | 1985-11-11 |
| FR2456101B1 (en]) | 1985-04-05 |
| IL59967A (en) | 1984-05-31 |
| AT377261B (de) | 1985-02-25 |
| FR2456101A1 (fr) | 1980-12-05 |
| FI68825B (fi) | 1985-07-31 |
| PL124035B1 (en) | 1982-12-31 |
| PT71213A (en) | 1980-06-01 |
| CA1141379A (en) | 1983-02-15 |
| JPS5615286A (en) | 1981-02-14 |
| DD150605A5 (de) | 1981-09-09 |
| SU1151210A3 (ru) | 1985-04-15 |
| NL8002678A (nl) | 1980-11-13 |
| GR68518B (en]) | 1982-01-11 |
| DE3017564A1 (de) | 1980-11-13 |
| ES8102570A1 (es) | 1981-02-16 |
| LU82437A1 (fr) | 1980-07-31 |
| GB2051048B (en) | 1983-01-19 |
| NO152607B (no) | 1985-07-15 |
| GB2051048A (en) | 1981-01-14 |
| IT1133085B (it) | 1986-07-09 |
| CS325880A2 (en) | 1985-06-13 |
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