DE69616801T2 - Eintopfverfahren zur herstellung von 2-oxazolidinonderivate - Google Patents
Eintopfverfahren zur herstellung von 2-oxazolidinonderivateInfo
- Publication number
- DE69616801T2 DE69616801T2 DE69616801T DE69616801T DE69616801T2 DE 69616801 T2 DE69616801 T2 DE 69616801T2 DE 69616801 T DE69616801 T DE 69616801T DE 69616801 T DE69616801 T DE 69616801T DE 69616801 T2 DE69616801 T2 DE 69616801T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- preparing
- carried out
- methyl ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000005580 one pot reaction Methods 0.000 title claims description 13
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical group CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 claims description 8
- BXCCIZOPQQWMKN-ZDUSSCGKSA-N methyl (2s)-2-(butoxycarbonylamino)-3-(4-nitrophenyl)propanoate Chemical compound CCCCOC(=O)N[C@H](C(=O)OC)CC1=CC=C([N+]([O-])=O)C=C1 BXCCIZOPQQWMKN-ZDUSSCGKSA-N 0.000 claims description 8
- BTHMRXRBXYHLRA-FVGYRXGTSA-N methyl (2s)-2-amino-3-(4-nitrophenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 BTHMRXRBXYHLRA-FVGYRXGTSA-N 0.000 claims description 8
- OSUKKPIXRGNCBB-ZDUSSCGKSA-N butyl n-[(2s)-1-(4-aminophenyl)-3-hydroxypropan-2-yl]carbamate Chemical compound CCCCOC(=O)N[C@H](CO)CC1=CC=C(N)C=C1 OSUKKPIXRGNCBB-ZDUSSCGKSA-N 0.000 claims description 7
- RPGKNZIGMYPYML-ZDUSSCGKSA-N methyl (2s)-3-(4-aminophenyl)-2-(butoxycarbonylamino)propanoate Chemical compound CCCCOC(=O)N[C@H](C(=O)OC)CC1=CC=C(N)C=C1 RPGKNZIGMYPYML-ZDUSSCGKSA-N 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 6
- WNAVSKJKDPLWBD-VIFPVBQESA-N (4s)-4-[(4-aminophenyl)methyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(N)=CC=C1C[C@@H]1NC(=O)OC1 WNAVSKJKDPLWBD-VIFPVBQESA-N 0.000 claims description 5
- 238000006641 Fischer synthesis reaction Methods 0.000 claims description 5
- 239000012954 diazonium Substances 0.000 claims description 5
- 150000001989 diazonium salts Chemical class 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- IMAZLPMRHTYSQZ-WWPIYYJJSA-N hydrazine (4S)-4-[(4-hydrazinylphenyl)methyl]-1,3-oxazolidin-2-one hydrochloride Chemical compound Cl.NN.C1=CC(NN)=CC=C1C[C@@H]1NC(=O)OC1 IMAZLPMRHTYSQZ-WWPIYYJJSA-N 0.000 claims description 2
- 125000004492 methyl ester group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 229910001868 water Inorganic materials 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 235000010265 sodium sulphite Nutrition 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 229910052681 coesite Inorganic materials 0.000 description 4
- 229910052906 cristobalite Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000018 receptor agonist Substances 0.000 description 4
- 229940044601 receptor agonist Drugs 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 229910052682 stishovite Inorganic materials 0.000 description 4
- 229910052905 tridymite Inorganic materials 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- GTVVZTAFGPQSPC-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-nitrophenyl)propanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-QMMMGPOBSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- JLDUTSKKXXJGGG-IHRRRGAJSA-N C1[C@@H](N(C)C)C[C@@H]1C(C1=C2)=CNC1=CC=C2C[C@@H]1NC(=O)OC1 Chemical compound C1[C@@H](N(C)C)C[C@@H]1C(C1=C2)=CNC1=CC=C2C[C@@H]1NC(=O)OC1 JLDUTSKKXXJGGG-IHRRRGAJSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 2
- ITXICYVPEAFHQO-SRVKXCTJSA-N C1[C@@H](N)C[C@@H]1C(C1=C2)=CNC1=CC=C2C[C@@H]1NC(=O)OC1 Chemical compound C1[C@@H](N)C[C@@H]1C(C1=C2)=CNC1=CC=C2C[C@@H]1NC(=O)OC1 ITXICYVPEAFHQO-SRVKXCTJSA-N 0.000 description 2
- 208000006561 Cluster Headache Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- BKMMTJMQCTUHRP-VKHMYHEASA-N (S)-2-aminopropan-1-ol Chemical group C[C@H](N)CO BKMMTJMQCTUHRP-VKHMYHEASA-N 0.000 description 1
- 102000035038 5-HT1 receptors Human genes 0.000 description 1
- 108091005478 5-HT1 receptors Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000007433 nerve pathway Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- IZGYIFFQBZWOLJ-CKAACLRMSA-N phaseic acid Chemical compound C1C(=O)C[C@@]2(C)OC[C@]1(C)[C@@]2(O)C=CC(/C)=C\C(O)=O IZGYIFFQBZWOLJ-CKAACLRMSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- ULSDMUVEXKOYBU-ZDUSSCGKSA-N zolmitriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C[C@H]1COC(=O)N1 ULSDMUVEXKOYBU-ZDUSSCGKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (16)
1. Verfahren zur Herstellung einer Verbindung der
Formel (I)
worin
R¹ und R² jeweils unabhängig voneinander für Wasserstoff
oder C&sub1;&submin;&sub4;-Alkyl stehen oder zu einem Azetidinring
verknüpft sind und
A für C&sub3;&submin;&sub6;-Cycloalkyl, C&sub1;&submin;&sub3;-Alkyl-C&sub3;&submin;&sub6;-cycloalkyl oder C&sub2;-
Alkyl steht,
mit der Maßgabe, daß A nicht für C&sub2;-Alkyl steht, wenn R¹
und R² beide für Methyl stehen;
bei dem man
a) aus
4-Nitro-(L)-phenylalaninmethylesterhydrochlorid der Formel (II)
durch Zusatz von Natriumcarbonat oder
Natriumhydrogencarbonat und
Chlorameisensäuren-butylester ein Carbamat bildet und zu (S)-N-
Butoxycarbonyl-4-nitrophenylalaninmethylester
der Formel (III)
umsetzt;
b) die Verbindung der Formel (III) zu (S)-N-
Butoxycarbonyl-4-aminophenylalaninmethylester
der Formel (IV)
reduziert;
c) die Methylestergruppierung -CO&sub2;CH&sub3; in der
Verbindung der Formel (IV) unter Bildung von
(S)-N-Butoxycarbonyl-4-aminophenylalaninol der
Formel (V)
reduziert;
d) die Verbindung der Formel (V) durch Ringschluß
in (S)-4-(4-Aminobenzyl)-2-oxazolidinon der
Formel (VI)
überführt;
e) das Diazoniumsalz der Verbindung der Formel
(VI) herstellt und danach zum Hydrazin (S)-4-
(4-Hydrazinobenzyl)-2-oxazolidinon-hydrochlorid
der Formel (VII)
reduziert;
f) die Verbindung der Formel (VII) durch Fischer-
Reaktion in die Verbindung der Formel (I)
überführt,
und einen oder mehrere der Schritte a) bis f) nach
einem Eintopfverfahren durchführt.
2. Verfahren nach Anspruch 1 zur Herstellung einer
Verbindung der Formel (I), worin A für Cyclobutyl
steht.
3. Verfahren nach Anspruch 2 zur Herstellung von
4-[3-(3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-
ylmethyl]-(4S)oxazolidin-2-on.
4. Verfahren nach einem der Ansprüche 1 bis 3, bei
dem man die Schritte (a) bis (d) nach einem
Eintopfverfahren durchführt, danach die Verbindung der
Formel (VI) isoliert und ein zweites Eintopfverfahren
für die Schritte (e) und (f) durchführt.
5. Zwischenprodukt der Formel (III)
6. Zwischenprodukt der Formel (IV)
7. Zwischenprodukt der Formel (V)
8. Zwischenprodukt der Formel (VI)
9. Verfahren zur Herstellung einer Verbindung der
Formel (III)
bei dem man eine Verbindung der Formel (II)
mit Natriumcarbonat und Chlorameisensäure-n-butylester
umsetzt.
10. Verfahren zur Herstellung einer Verbindung der
Formel (IV)
bei dem man eine Verbindung der Formel (III)
reduziert.
11. Verfahren zur Herstellung einer Verbindung der
Formel (V)
bei dem man eine Verbindung der Formel (IV)
reduziert.
12. Verfahren zur Herstellung einer Verbindung der
Formel (VI)
bei dem man eine Verbindung der Formel (V)
einem Ringschluß unterwirft.
13. Verwendung eines Zwischenprodukts nach Anspruch
5 bei der Herstellung einer eine Verbindung der Formel
(I) nach Anspruch 1 enthaltenden Zusammensetzung zur
Verwendung in der Medizin.
14. Verwendung eines Zwischenprodukts nach Anspruch
6 bei der Herstellung einer eine Verbindung der Formel
(I) nach Anspruch 1 enthaltenden Zusammensetzung zur
Verwendung in der Medizin.
15. Verwendung eines Zwischenprodukts nach Anspruch
8 bei der Herstellung einer eine Verbindung der Formel
(I) nach Anspruch 1 enthaltenden Zusammensetzung zur
Verwendung in der Medizin.
16. Verwendung nach einem der Ansprüche 13 bis 15,
bei der die Zusammensetzung zur Verwendung bei der
Behandlung und Prophylaxe von Migräne vorgesehen ist.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9516143.6A GB9516143D0 (en) | 1995-08-07 | 1995-08-07 | Improved chemical synthesis |
| PCT/GB1996/001886 WO1997006163A1 (en) | 1995-08-07 | 1996-08-02 | One pot synthesis of 2-oxazolidinone derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69616801D1 DE69616801D1 (de) | 2001-12-13 |
| DE69616801T2 true DE69616801T2 (de) | 2002-06-06 |
Family
ID=10778865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69616801T Expired - Lifetime DE69616801T2 (de) | 1995-08-07 | 1996-08-02 | Eintopfverfahren zur herstellung von 2-oxazolidinonderivate |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6303791B1 (de) |
| EP (1) | EP0843673B1 (de) |
| JP (2) | JP3729504B2 (de) |
| AT (1) | ATE208388T1 (de) |
| AU (1) | AU6663596A (de) |
| DE (1) | DE69616801T2 (de) |
| GB (1) | GB9516143D0 (de) |
| WO (1) | WO1997006163A1 (de) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1799675A4 (de) * | 2004-04-22 | 2010-04-28 | Reddys Lab Ltd Dr | Verfahren zur herstellung von optisch reinem zolmitriptan |
| US20050245585A1 (en) * | 2004-04-22 | 2005-11-03 | Islam Aminul | Process for preparing optically pure zolmitriptan |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8724912D0 (en) | 1987-10-23 | 1987-11-25 | Wellcome Found | Indole derivatives |
| HU219974B (hu) | 1990-06-07 | 2001-10-28 | Astrazeneca Ab, | Heterociklusos csoporttal helyettesített indolszármazék, előállítása és a vegyületet hatóanyagként tartalmazó gyógyszerkészítmények |
| GB9401436D0 (en) | 1994-01-26 | 1994-03-23 | Wellcome Found | Therapeutic heterocyclic compounds |
-
1995
- 1995-08-07 GB GBGB9516143.6A patent/GB9516143D0/en active Pending
-
1996
- 1996-08-02 US US09/011,044 patent/US6303791B1/en not_active Expired - Lifetime
- 1996-08-02 JP JP50822797A patent/JP3729504B2/ja not_active Expired - Lifetime
- 1996-08-02 DE DE69616801T patent/DE69616801T2/de not_active Expired - Lifetime
- 1996-08-02 EP EP96926466A patent/EP0843673B1/de not_active Expired - Lifetime
- 1996-08-02 AU AU66635/96A patent/AU6663596A/en not_active Abandoned
- 1996-08-02 WO PCT/GB1996/001886 patent/WO1997006163A1/en not_active Ceased
- 1996-08-02 AT AT96926466T patent/ATE208388T1/de active
-
2002
- 2002-03-26 JP JP2002087016A patent/JP2002308874A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DE69616801D1 (de) | 2001-12-13 |
| ATE208388T1 (de) | 2001-11-15 |
| JPH11510805A (ja) | 1999-09-21 |
| JP2002308874A (ja) | 2002-10-23 |
| AU6663596A (en) | 1997-03-05 |
| EP0843673B1 (de) | 2001-11-07 |
| GB9516143D0 (en) | 1995-10-04 |
| US6303791B1 (en) | 2001-10-16 |
| EP0843673A1 (de) | 1998-05-27 |
| JP3729504B2 (ja) | 2005-12-21 |
| WO1997006163A1 (en) | 1997-02-20 |
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