NO162383B - Analogifremgangsmaate for fremstilling av farmakologisk aktive 1,3-dioksan-5-yl-alkensyrer. - Google Patents
Analogifremgangsmaate for fremstilling av farmakologisk aktive 1,3-dioksan-5-yl-alkensyrer. Download PDFInfo
- Publication number
- NO162383B NO162383B NO831679A NO831679A NO162383B NO 162383 B NO162383 B NO 162383B NO 831679 A NO831679 A NO 831679A NO 831679 A NO831679 A NO 831679A NO 162383 B NO162383 B NO 162383B
- Authority
- NO
- Norway
- Prior art keywords
- formula
- phenyl
- hydroxy
- compound
- cis
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 82
- 239000002253 acid Substances 0.000 title claims description 46
- 238000002360 preparation method Methods 0.000 title claims description 19
- 150000007513 acids Chemical class 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 83
- -1 nitro, hydroxy Chemical group 0.000 claims description 81
- 239000000203 mixture Substances 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 239000007858 starting material Substances 0.000 claims description 33
- 229910052705 radium Inorganic materials 0.000 claims description 31
- 229910052701 rubidium Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 239000002585 base Substances 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 10
- 229920002554 vinyl polymer Polymers 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- PSZDOEIIIJFCFE-OSQDELBUSA-N erythrodiol Chemical class C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(CO)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C PSZDOEIIIJFCFE-OSQDELBUSA-N 0.000 claims description 8
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 7
- 239000005977 Ethylene Substances 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
- 125000000532 dioxanyl group Chemical group 0.000 claims description 7
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- PSZDOEIIIJFCFE-UHFFFAOYSA-N Oleanolic alcohol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(CO)CCC(C)(C)CC5C4=CCC3C21C PSZDOEIIIJFCFE-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- HTZRWCSRPTWJCT-UHFFFAOYSA-N erythrodiol Natural products CC1(C)CCC2(CO)CCC3C(CCC4C3(C)CCC5C(C)(C)C(O)CCC45C)C2C1 HTZRWCSRPTWJCT-UHFFFAOYSA-N 0.000 claims description 6
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012024 dehydrating agents Substances 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 150000002373 hemiacetals Chemical class 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 11
- 238000010640 amide synthesis reaction Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 128
- 238000005481 NMR spectroscopy Methods 0.000 description 102
- 239000000243 solution Substances 0.000 description 101
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
- 239000003921 oil Substances 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 43
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 32
- 239000012230 colorless oil Substances 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 238000004440 column chromatography Methods 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 235000002639 sodium chloride Nutrition 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 150000001299 aldehydes Chemical class 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000003085 diluting agent Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 11
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- 229940035437 1,3-propanediol Drugs 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000006188 syrup Substances 0.000 description 8
- 235000020357 syrup Nutrition 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 230000001631 hypertensive effect Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 4
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 238000004452 microanalysis Methods 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 3
- CRZJPEIBPQWDGJ-UHFFFAOYSA-N 2-chloro-1,1-dimethoxyethane Chemical compound COC(CCl)OC CRZJPEIBPQWDGJ-UHFFFAOYSA-N 0.000 description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring 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
- A61P11/08—Bronchodilators
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8213702 | 1982-05-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO831679L NO831679L (no) | 1983-11-14 |
| NO162383B true NO162383B (no) | 1989-09-11 |
Family
ID=10530304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO831679A NO162383B (no) | 1982-05-12 | 1983-05-11 | Analogifremgangsmaate for fremstilling av farmakologisk aktive 1,3-dioksan-5-yl-alkensyrer. |
Country Status (32)
| Country | Link |
|---|---|
| US (3) | US4567197A (pl) |
| EP (1) | EP0094239B1 (pl) |
| JP (1) | JPS58222081A (pl) |
| KR (1) | KR880002001B1 (pl) |
| AR (1) | AR240817A1 (pl) |
| AT (1) | ATE28329T1 (pl) |
| AU (1) | AU562056B2 (pl) |
| CA (4) | CA1258464A (pl) |
| CS (2) | CS245795B2 (pl) |
| CY (1) | CY1453A (pl) |
| DD (2) | DD219769A5 (pl) |
| DE (1) | DE3372483D1 (pl) |
| DK (1) | DK163431C (pl) |
| ES (4) | ES8407038A1 (pl) |
| FI (1) | FI80027C (pl) |
| GB (1) | GB8310407D0 (pl) |
| GR (1) | GR78138B (pl) |
| HK (1) | HK17889A (pl) |
| HU (1) | HU198705B (pl) |
| IE (1) | IE55114B1 (pl) |
| IL (1) | IL68628A0 (pl) |
| KE (1) | KE3823A (pl) |
| MW (1) | MW1583A1 (pl) |
| NO (1) | NO162383B (pl) |
| NZ (1) | NZ204202A (pl) |
| PH (1) | PH21691A (pl) |
| PL (3) | PL140274B1 (pl) |
| PT (1) | PT76684B (pl) |
| SG (1) | SG57088G (pl) |
| SU (1) | SU1277893A3 (pl) |
| ZA (1) | ZA833179B (pl) |
| ZW (1) | ZW10083A1 (pl) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8310407D0 (en) * | 1982-05-12 | 1983-05-25 | Ici Plc | 1 3 - dioxan -5- ylalkenoic acids |
| FR2551446B1 (fr) * | 1983-08-31 | 1987-03-20 | Elf Aquitaine | Compositions de resines ayant une resistance amelioree au choc renfermant un polymere thermoplastique, un additif choc du type copolymere greffe, et eventuellement d'autres additifs, et copolymere greffe correspondant, a caractere d'additif choc |
| GB8330097D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Cyclic ethers |
| GB8330094D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Diphenyl compounds |
| GB8330120D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Chemical process |
| GB8417314D0 (en) * | 1984-07-06 | 1984-08-08 | Ici Plc | Carboxylic acid derivatives |
| DK212786A (da) * | 1985-05-10 | 1986-11-11 | Ici Plc | 1,3-dioxanethere |
| GB8511891D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Alkenoic acids |
| GB8511897D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Carboxylic acids |
| GB8511890D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Benzene derivatives |
| GB8511892D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Fluoralkane derivatives |
| EP0201352B1 (en) * | 1985-05-10 | 1992-06-24 | Imperial Chemical Industries Plc | Alkene derivatives |
| GB8511894D0 (en) | 1985-05-10 | 1985-06-19 | Ici Plc | Phenol derivatives |
| GB8511895D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Heterocyclic compounds |
| GB8611174D0 (en) * | 1986-05-08 | 1986-06-18 | Ici Plc | Amide derivatives |
| WO1987002983A1 (en) * | 1985-11-12 | 1987-05-21 | Imperial Chemical Industries Plc | Amide derivatives |
| GB8531892D0 (en) * | 1985-12-30 | 1986-02-05 | Ici Plc | Carboxylic acids |
| DE3603662A1 (de) * | 1986-02-06 | 1987-08-13 | Basf Ag | Acetalisierte oder ketalisierte dihydroxyaldehyde, verfahren zu ihrer herstellung und diese enthaltende loesungen |
| GB8626296D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Therapeutic agents |
| GB8626297D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Pharmaceutical compositions |
| GB8709794D0 (en) * | 1987-04-24 | 1987-05-28 | Ici Plc | Heterocyclic acids |
| US5248780A (en) * | 1988-02-16 | 1993-09-28 | Imperial Chemical Industries, Plc | Pyridyl substituted alkenoic acid derivatives |
| GB8901201D0 (en) * | 1988-02-16 | 1989-03-15 | Ici Plc | Pyridine derivatives |
| EP0346511A1 (en) * | 1988-06-15 | 1989-12-20 | Fujisawa Pharmaceutical Co., Ltd. | Oxygen-containing hererocyclic compound, processes for their preparation and pharmaceutical compositions comprising them |
| CN1034120C (zh) * | 1988-10-21 | 1997-02-26 | 曾尼卡有限公司 | 制备二噁烷链烯酸衍生物的方法 |
| IE81170B1 (en) * | 1988-10-21 | 2000-05-31 | Zeneca Ltd | Pyridine derivatives |
| GB9021571D0 (en) * | 1990-10-04 | 1990-11-21 | Ici Plc | Heterocyclic acids |
| US5925795A (en) * | 1996-09-16 | 1999-07-20 | Zeneca Limited | Processes for the preparation of aryl-β-diketones, arylpyrimidine ketones and crop protection intermediates |
| GB0413970D0 (en) * | 2004-06-22 | 2004-07-28 | Syngenta Participations Ag | Chemical compounds |
| US20110178112A1 (en) * | 2006-01-18 | 2011-07-21 | Evolva Sa | PPAR Modulators |
| JP2010516700A (ja) * | 2007-01-18 | 2010-05-20 | エヴォルヴァ エスアー | 置換１，３−ジオキサンおよびそれらの使用 |
| AU2008206047B2 (en) * | 2007-01-18 | 2014-07-10 | Evolva Sa | Substituted 1,3-dioxanes useful as PPAR modulators |
| AU2013261719B2 (en) * | 2012-05-18 | 2017-07-27 | Sanofi | Benzo[1,3]dioxine derivatives and their use as LPAR5 antagonists |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4243592A (en) * | 1979-03-12 | 1981-01-06 | The Upjohn Company | 9,11-Dideoxy-10-oxa-TXB compounds |
| GB8310407D0 (en) * | 1982-05-12 | 1983-05-25 | Ici Plc | 1 3 - dioxan -5- ylalkenoic acids |
| GB8417314D0 (en) * | 1984-07-06 | 1984-08-08 | Ici Plc | Carboxylic acid derivatives |
-
1983
- 1983-04-18 GB GB838310407A patent/GB8310407D0/en active Pending
- 1983-04-29 ZW ZW100/83A patent/ZW10083A1/xx unknown
- 1983-05-02 IE IE1005/83A patent/IE55114B1/en not_active IP Right Cessation
- 1983-05-04 AU AU14223/83A patent/AU562056B2/en not_active Ceased
- 1983-05-04 ZA ZA833179A patent/ZA833179B/xx unknown
- 1983-05-04 MW MW15/83A patent/MW1583A1/xx unknown
- 1983-05-06 US US06/492,247 patent/US4567197A/en not_active Expired - Fee Related
- 1983-05-09 HU HU831588A patent/HU198705B/hu not_active IP Right Cessation
- 1983-05-09 DE DE8383302613T patent/DE3372483D1/de not_active Expired
- 1983-05-09 AT AT83302613T patent/ATE28329T1/de not_active IP Right Cessation
- 1983-05-09 EP EP83302613A patent/EP0094239B1/en not_active Expired
- 1983-05-09 IL IL68628A patent/IL68628A0/xx not_active IP Right Cessation
- 1983-05-11 PL PL1983241920A patent/PL140274B1/pl unknown
- 1983-05-11 PH PH28883A patent/PH21691A/en unknown
- 1983-05-11 NZ NZ204202A patent/NZ204202A/en unknown
- 1983-05-11 NO NO831679A patent/NO162383B/no unknown
- 1983-05-11 GR GR71324A patent/GR78138B/el unknown
- 1983-05-11 CA CA000427937A patent/CA1258464A/en not_active Expired
- 1983-05-11 SU SU833596399A patent/SU1277893A3/ru active
- 1983-05-11 PL PL1983250098A patent/PL140462B1/pl unknown
- 1983-05-11 PL PL1983250099A patent/PL140463B1/pl unknown
- 1983-05-11 DK DK211883A patent/DK163431C/da not_active IP Right Cessation
- 1983-05-12 JP JP58083438A patent/JPS58222081A/ja active Granted
- 1983-05-12 CS CS847257A patent/CS245795B2/cs unknown
- 1983-05-12 ES ES522331A patent/ES8407038A1/es not_active Expired
- 1983-05-12 DD DD83264391A patent/DD219769A5/de not_active IP Right Cessation
- 1983-05-12 AR AR293002A patent/AR240817A1/es active
- 1983-05-12 DD DD83250869A patent/DD212515A5/de not_active IP Right Cessation
- 1983-05-12 PT PT76684A patent/PT76684B/pt not_active IP Right Cessation
- 1983-05-12 FI FI831664A patent/FI80027C/fi not_active IP Right Cessation
- 1983-05-12 CS CS833336A patent/CS245783B2/cs unknown
- 1983-05-12 KR KR1019830002053A patent/KR880002001B1/ko not_active IP Right Cessation
- 1983-12-30 ES ES528576A patent/ES8700250A1/es not_active Expired
- 1983-12-30 ES ES528577A patent/ES8608507A1/es not_active Expired
- 1983-12-30 ES ES528575A patent/ES8700249A1/es not_active Expired
-
1985
- 1985-11-12 US US06/797,204 patent/US4745198A/en not_active Expired - Fee Related
-
1988
- 1988-02-09 US US07/153,928 patent/US5166377A/en not_active Expired - Fee Related
- 1988-08-18 KE KE3823A patent/KE3823A/xx unknown
- 1988-08-31 SG SG570/88A patent/SG57088G/en unknown
-
1989
- 1989-03-02 HK HK178/89A patent/HK17889A/xx unknown
- 1989-05-24 CA CA000600593A patent/CA1269109A/en not_active Expired - Fee Related
- 1989-05-24 CA CA000600591A patent/CA1268771A/en not_active Expired - Fee Related
- 1989-05-24 CA CA000600592A patent/CA1268772A/en not_active Expired - Fee Related
- 1989-07-21 CY CY1453A patent/CY1453A/xx unknown
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