NZ512935A - Synthesis of histamine dihydrochloride - Google Patents
Synthesis of histamine dihydrochlorideInfo
- Publication number
- NZ512935A NZ512935A NZ512935A NZ51293599A NZ512935A NZ 512935 A NZ512935 A NZ 512935A NZ 512935 A NZ512935 A NZ 512935A NZ 51293599 A NZ51293599 A NZ 51293599A NZ 512935 A NZ512935 A NZ 512935A
- Authority
- NZ
- New Zealand
- Prior art keywords
- histamine
- solution
- hydrogen chloride
- histamine dihydrochloride
- dihydrochloride
- Prior art date
Links
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 229960004931 histamine dihydrochloride Drugs 0.000 title claims abstract description 83
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 27
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 80
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 77
- 239000012535 impurity Substances 0.000 claims abstract description 75
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 61
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 61
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 50
- 229960002885 histidine Drugs 0.000 claims abstract description 34
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 28
- IVCJGQQPPHYHBS-UHFFFAOYSA-N 2-(1h-imidazol-5-yl)ethanamine;hydrochloride Chemical compound Cl.NCCC1=CN=CN1 IVCJGQQPPHYHBS-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 97
- 229960001340 histamine Drugs 0.000 claims description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 41
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 claims description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 40
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 30
- 238000006114 decarboxylation reaction Methods 0.000 claims description 28
- 239000003054 catalyst Substances 0.000 claims description 22
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 15
- 239000012458 free base Substances 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 13
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 claims description 11
- -1 L-histidine HCI monohydrate Chemical class 0.000 claims description 9
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 claims description 6
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 claims description 6
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 6
- 239000012965 benzophenone Substances 0.000 claims description 6
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 claims description 5
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 claims description 5
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 5
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 5
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 229960000645 histamine hydrochloride Drugs 0.000 claims 1
- XEJCDBUNISUVGZ-XRIGFGBMSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)[C@@H](N)CC1=CN=CN1 XEJCDBUNISUVGZ-XRIGFGBMSA-N 0.000 abstract 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 abstract 1
- 229960003446 histidine monohydrochloride Drugs 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 53
- 239000000047 product Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 31
- 239000000725 suspension Substances 0.000 description 30
- 239000012467 final product Substances 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000002253 acid Substances 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000012065 filter cake Substances 0.000 description 18
- 150000003839 salts Chemical group 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 16
- 238000003556 assay Methods 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 10
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 9
- 239000000356 contaminant Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 239000006184 cosolvent Substances 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- OUCSEDFVYPBLLF-KAYWLYCHSA-N 5-(4-fluorophenyl)-1-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-n,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 OUCSEDFVYPBLLF-KAYWLYCHSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940093476 ethylene glycol Drugs 0.000 description 2
- AKRQHOWXVSDJEF-UHFFFAOYSA-N heptane-1-sulfonic acid Chemical compound CCCCCCCS(O)(=O)=O AKRQHOWXVSDJEF-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- ZXDDPOHVAMWLBH-UHFFFAOYSA-N 2,4-Dihydroxybenzophenone Chemical compound OC1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 ZXDDPOHVAMWLBH-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- CMXXUDSWGMGYLZ-UHFFFAOYSA-N 2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride;hydrate Chemical compound O.Cl.OC(=O)C(N)CC1=CN=CN1 CMXXUDSWGMGYLZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- QZNNVYOVQUKYSC-UHFFFAOYSA-N L-hystidine hydrochloride Chemical compound [Cl-].OC(=O)C([NH3+])CC1=CN=CN1 QZNNVYOVQUKYSC-UHFFFAOYSA-N 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
- 229940050865 sodium phosphate,monobasic,monohydrate Drugs 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11393398P | 1998-12-23 | 1998-12-23 | |
| PCT/US1999/030379 WO2000039098A1 (en) | 1998-12-23 | 1999-12-20 | Synthesis of histamine dihydrochloride |
| US09/467,652 US6403806B1 (en) | 1998-12-23 | 1999-12-20 | Synthesis of histamine dihydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ512935A true NZ512935A (en) | 2003-08-29 |
Family
ID=26811642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ512935A NZ512935A (en) | 1998-12-23 | 1999-12-20 | Synthesis of histamine dihydrochloride |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US6403806B1 (enExample) |
| EP (1) | EP1140857B1 (enExample) |
| JP (1) | JP4139082B2 (enExample) |
| CN (1) | CN1155579C (enExample) |
| AT (1) | ATE399769T1 (enExample) |
| AU (1) | AU763523B2 (enExample) |
| CA (1) | CA2356871C (enExample) |
| DE (1) | DE69939027D1 (enExample) |
| DK (1) | DK1140857T3 (enExample) |
| ES (1) | ES2310056T3 (enExample) |
| HK (1) | HK1040998B (enExample) |
| IL (2) | IL143570A0 (enExample) |
| NZ (1) | NZ512935A (enExample) |
| PT (1) | PT1140857E (enExample) |
| TW (1) | TWI243166B (enExample) |
| WO (1) | WO2000039098A1 (enExample) |
| ZA (1) | ZA200104552B (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6590106B2 (en) * | 1997-05-09 | 2003-07-08 | Pharm-Eco Laboratories, Inc. | Amino acid derivatives and methods of making the same |
| US7728015B2 (en) * | 2004-04-22 | 2010-06-01 | Mor Research Applications Ltd. | Compositions for weight management |
| WO2005101979A2 (en) * | 2004-04-22 | 2005-11-03 | Mor Research Applications Ltd. | Method of food intake management |
| US20080051440A1 (en) * | 2004-04-22 | 2008-02-28 | Mor Research Applications Ltd. | Compositions for weight management |
| US20060188528A1 (en) * | 2005-02-23 | 2006-08-24 | Ansell Healthcare Products Llc | Spreadable warming lubricant |
| US7709428B2 (en) * | 2005-02-23 | 2010-05-04 | Ansell Healthcare Products Llc | Thickened spreadable warming lubricant |
| DE102006060908A1 (de) * | 2006-12-20 | 2008-07-03 | Evonik Degussa Gmbh | Kontinuierliches Verfahren zur Decarboxylierung von Carbonsäuren |
| US8770201B2 (en) * | 2007-10-26 | 2014-07-08 | Glycobiosciences Inc. | Condom with multifunctional coating |
| CN102477014B (zh) * | 2010-11-27 | 2015-08-19 | 山东新时代药业有限公司 | 二盐酸组胺的制备方法 |
| ITMI20110379A1 (it) * | 2011-03-10 | 2012-09-11 | Erregierre Spa | Procedimento per la preparazione di istamina dicloridrato con elevato grado di purezza |
| US9452954B2 (en) | 2013-03-14 | 2016-09-27 | University Of Georgia Research Foundation, Inc. | Method for decarboxylation of amino acids via imine formation |
| US10487042B2 (en) | 2013-03-14 | 2019-11-26 | University Of Georgia Research Foundation, Inc. | Method for solvent-free decarboxylation of amino acids via imine formation |
| US10118898B2 (en) | 2013-03-14 | 2018-11-06 | University Of Georgia Research Foundation, Inc. | Method for decarboxylation of amino acids via imine formation |
| CN103288742A (zh) * | 2013-06-04 | 2013-09-11 | 四川百利药业有限责任公司 | 一种高纯度英加韦林原料的制备方法 |
| CN103739551B (zh) * | 2013-09-24 | 2016-03-23 | 国药一心制药有限公司 | 一种二盐酸组胺的纯化方法 |
| JP6495288B2 (ja) | 2013-12-17 | 2019-04-03 | サイモン フレーザー ユニバーシティー | トコジラミを誘引および／または拘束するための化合物、組成物、および方法 |
| CN103739552B (zh) * | 2014-01-24 | 2015-08-26 | 国药一心制药有限公司 | 二盐酸组胺的制备方法 |
| CN104402825B (zh) * | 2014-12-13 | 2017-03-15 | 济南诚汇双达化工有限公司 | 一种组胺二盐酸盐的合成方法 |
| CN106432089B (zh) * | 2016-09-12 | 2018-09-07 | 开封制药(集团)有限公司 | 二盐酸组胺的合成方法 |
| US10889549B2 (en) | 2017-07-03 | 2021-01-12 | Jubilant Generics Limited | Continuous process for the preparation of 2-(1H-imidazol-4-yl) ethanamine and pharmaceutically acceptable salts thereof |
| WO2019008594A1 (en) * | 2017-07-03 | 2019-01-10 | Jubilant Generics Limited | CONTINUOUS PROCESS FOR THE PREPARATION OF 2- (1H-IMIDAZOL-4-YL) ETHANAMINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS |
| CN112266360B (zh) * | 2020-10-26 | 2022-06-10 | 武汉桀升生物科技有限公司 | 一种高纯度组胺二盐酸盐的合成方法 |
| CN113045500A (zh) * | 2021-03-31 | 2021-06-29 | 苏州园方生物科技有限公司 | 一种组胺二盐酸盐的制备方法 |
| JP7193815B1 (ja) | 2021-12-28 | 2022-12-21 | Ｋｍバイオロジクス株式会社 | ヒスタミンの製造方法及び医薬品としてのその使用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE57638C (de) | O. ECKARDT in Berlin j N.W., Bandelslr. 14 | Verfahren zur Herstellung von Steinkohlenbriquettes auf kaltem Wege | ||
| GB430108A (en) * | 1934-02-23 | 1935-06-13 | Boot S Pure Drug Company Ltd | Improvements relating to the preparation of histamine and its derivatives |
| GB1008594A (en) | 1963-07-03 | 1965-10-27 | Nat Res Dev | Process for the production of amines |
| SU557755A3 (ru) * | 1968-08-19 | 1977-05-05 | Янссен Фармасьютика Н.В. (Фирма) | Способ получени производных имидазола |
| DE3322117A1 (de) * | 1983-06-20 | 1984-12-20 | Diamalt AG, 8000 München | Verfahren zur herstellung von n(pfeil hoch)(tau)(pfeil hoch)-substituierten histidinderivaten, n(pfeil hoch)(tau)(pfeil hoch)-substituierten histidinderivate und ihre verwendung |
| NL8800998A (nl) * | 1988-04-18 | 1989-11-16 | Cedona Pharm Bv | Werkwijze voor het bereiden van een al of niet gesubstitueerd 4(5)-(omega-aminoalkyl) imidazool. |
| JPH05255204A (ja) * | 1992-03-11 | 1993-10-05 | Kanegafuchi Chem Ind Co Ltd | アミン類の製造法 |
| SE513429C2 (sv) | 1992-06-03 | 2000-09-11 | Syntello Inc | Preparat för aktivering av naturliga mördarceller, vilket preparat innehåller interferon alfa och biogena aminer |
-
1999
- 1999-12-20 DK DK99968148T patent/DK1140857T3/da active
- 1999-12-20 EP EP99968148A patent/EP1140857B1/en not_active Expired - Lifetime
- 1999-12-20 DE DE69939027T patent/DE69939027D1/de not_active Expired - Lifetime
- 1999-12-20 HK HK02102715.8A patent/HK1040998B/en not_active IP Right Cessation
- 1999-12-20 CA CA2356871A patent/CA2356871C/en not_active Expired - Lifetime
- 1999-12-20 NZ NZ512935A patent/NZ512935A/en not_active IP Right Cessation
- 1999-12-20 ES ES99968148T patent/ES2310056T3/es not_active Expired - Lifetime
- 1999-12-20 AT AT99968148T patent/ATE399769T1/de active
- 1999-12-20 WO PCT/US1999/030379 patent/WO2000039098A1/en not_active Ceased
- 1999-12-20 IL IL14357099A patent/IL143570A0/xx active IP Right Grant
- 1999-12-20 PT PT99968148T patent/PT1140857E/pt unknown
- 1999-12-20 CN CNB998149063A patent/CN1155579C/zh not_active Expired - Lifetime
- 1999-12-20 US US09/467,652 patent/US6403806B1/en not_active Expired - Fee Related
- 1999-12-20 JP JP2000591009A patent/JP4139082B2/ja not_active Expired - Fee Related
- 1999-12-20 AU AU24825/00A patent/AU763523B2/en not_active Expired
-
2000
- 2000-02-14 TW TW088122820A patent/TWI243166B/zh not_active IP Right Cessation
-
2001
- 2001-06-04 ZA ZA200104552A patent/ZA200104552B/en unknown
- 2001-06-05 IL IL143570A patent/IL143570A/en not_active IP Right Cessation
- 2001-10-09 US US09/974,469 patent/US6528654B2/en not_active Expired - Fee Related
-
2003
- 2003-02-10 US US10/364,810 patent/US6620942B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6528654B2 (en) | 2003-03-04 |
| EP1140857A1 (en) | 2001-10-10 |
| ZA200104552B (en) | 2002-01-16 |
| US6620942B2 (en) | 2003-09-16 |
| CA2356871A1 (en) | 2000-07-06 |
| DK1140857T3 (da) | 2008-10-20 |
| TWI243166B (en) | 2005-11-11 |
| AU763523B2 (en) | 2003-07-24 |
| HK1040998B (en) | 2009-04-24 |
| EP1140857B1 (en) | 2008-07-02 |
| CA2356871C (en) | 2010-09-14 |
| US6403806B1 (en) | 2002-06-11 |
| AU2482500A (en) | 2000-07-31 |
| IL143570A (en) | 2006-08-20 |
| CN1331681A (zh) | 2002-01-16 |
| JP2002533445A (ja) | 2002-10-08 |
| IL143570A0 (en) | 2002-04-21 |
| ATE399769T1 (de) | 2008-07-15 |
| PT1140857E (pt) | 2008-10-06 |
| HK1040998A1 (en) | 2002-06-28 |
| US20020035268A1 (en) | 2002-03-21 |
| ES2310056T3 (es) | 2008-12-16 |
| WO2000039098A9 (en) | 2001-05-17 |
| DE69939027D1 (de) | 2008-08-14 |
| JP4139082B2 (ja) | 2008-08-27 |
| WO2000039098A1 (en) | 2000-07-06 |
| CN1155579C (zh) | 2004-06-30 |
| US20030138964A1 (en) | 2003-07-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU763523B2 (en) | Synthesis of histamine dihydrochloride | |
| EP1543002B1 (en) | Preparation of 1h-imidazo 4,5-c|quinolin-4-amines via1h-imidazo 4,5-c|quinolin-4-phthalimide intermediates | |
| HU224914B1 (en) | Process for the preparation of nalbuphine having not more then 1% levels of beta-epimer | |
| JP2000517288A (ja) | Ｏ，ｏ’―ビスアロイル酒石酸類によるメチルフェニデートの光学分割 | |
| PL161779B1 (pl) | Sposób wytwarzania serynopochodnych zwiazku benzo /a/ naftacenowego PL PL PL PL PL | |
| OA10694A (en) | Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine. | |
| EP0361489A2 (en) | Novel 3,4-diaminoquinoline and pyridine compounds | |
| JP2927893B2 (ja) | フコシダーゼ阻害剤 | |
| NZ248776A (en) | Imidazole-substituted piperidine derivatives; pharmaceutical compositions and preparatory methods | |
| CA2629720A1 (en) | Synthesis and preparations of intermediates and polymorphs thereof useful for the preparation of donepezil hydrochloride | |
| EP1741701A1 (en) | Processes for producing 1-benzyl-4-¬(5,6-dimethoxy-1indanon)-2-yl|methylpiperidine and hydrochloride thereof | |
| US6177564B1 (en) | Process for the synthesis of N-benzyl-3-(4-fluorophenyl)-1-4-oxazin-2-one | |
| KR20010099867A (ko) | 히스타민 디하이드로클로라이드의 합성 방법 | |
| EP0369388A1 (en) | Hydroxy-1,2,3,4-tetrahydroaminoacridines, a process for their preparation and their use as medicaments | |
| CN114057725A (zh) | 一种酒石酸唑吡坦的合成方法 | |
| JPH07291943A (ja) | 光学活性Ｎ−ｔｅｒｔ−ブチル−２−ピペラジンカルボキサミドを製造する方法 | |
| JPH10507173A (ja) | レボブピバカインとその類似体のｌ−リシンからの製造法 | |
| JPH04364186A (ja) | スタウロスポリン誘導体および該化合物を有効成分とする血小板凝集阻害剤 | |
| AU2005317189A1 (en) | Process for the synthesis of (S)-1-(3,5-bis(trifluoromethyl)-phenyl)ethan-1-ol | |
| JPH0675510B2 (ja) | モラノリン誘導体の製法 | |
| MXPA98004820A (en) | Procedures and intermediates for preparing 1-bencil-4 - ((5,6-dimetoxi-1-indanon) -2-il) metilpiperid | |
| JPH10265506A (ja) | アセチル化シクロデキストリンの製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| ASS | Change of ownership |
Owner name: MEDA PHARMA S.A., LU Effective date: 20150219 |
|
| EXPY | Patent expired |