NO326458B1 - Substituerte benzofuranderivater, fremgangsmate for fremstilling derav, anvendelse av derivatene samt fremgangsmate for fremstilling av medikamenter - Google Patents

Info

Publication number

NO326458B1

NO326458B1 NO20015857A NO20015857A NO326458B1 NO 326458 B1 NO326458 B1 NO 326458B1 NO 20015857 A NO20015857 A NO 20015857A NO 20015857 A NO20015857 A NO 20015857A NO 326458 B1 NO326458 B1 NO 326458B1

Authority

NO

Norway

Prior art keywords

mmol

nmr

methoxy

hours

solution

Prior art date

2000-03-31

Links

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• 238000000034 method Methods 0.000 title claims description 102
• 238000002360 preparation method Methods 0.000 title claims description 31
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• 230000008569 process Effects 0.000 title claims description 9
• 229940079593 drug Drugs 0.000 title claims description 7
• 150000001907 coumarones Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 72
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 583
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 323
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 296
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 283
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 215
• 229910001868 water Inorganic materials 0.000 claims description 195
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 165
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 128
• 239000002904 solvent Substances 0.000 claims description 107
• 239000000203 mixture Substances 0.000 claims description 85
• 239000013078 crystal Substances 0.000 claims description 76
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 72
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 72
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 50
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 49
• 235000011114 ammonium hydroxide Nutrition 0.000 claims description 49
• 239000000725 suspension Substances 0.000 claims description 45
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• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 29
• 229910052799 carbon Inorganic materials 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
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• 238000000605 extraction Methods 0.000 claims description 7
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• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
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• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
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• 230000000607 poisoning effect Effects 0.000 claims description 4
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• 230000007103 stamina Effects 0.000 claims description 4
• 229940095064 tartrate Drugs 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 238000003776 cleavage reaction Methods 0.000 claims description 3
• 238000005516 engineering process Methods 0.000 claims description 3
• 125000005843 halogen group Chemical group 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 230000007017 scission Effects 0.000 claims description 3
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
• DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
• DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 2
• FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 claims description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• 125000000217 alkyl group Chemical group 0.000 claims description 2
• 230000008878 coupling Effects 0.000 claims description 2
• 238000010168 coupling process Methods 0.000 claims description 2
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• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000002757 morpholinyl group Chemical group 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
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• 235000002906 tartaric acid Nutrition 0.000 claims 2
• 239000011975 tartaric acid Substances 0.000 claims 2
• 150000003892 tartrate salts Chemical class 0.000 claims 1
• 239000000243 solution Substances 0.000 description 306
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 286
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 212
• 238000005160 1H NMR spectroscopy Methods 0.000 description 145
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 139
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• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
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• 238000000921 elemental analysis Methods 0.000 description 111
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