CZ20013431A3 - Způsob přípravy [S-(R*,S*)]-beta-[[[1-[1-oxo-3-(4-piperidinyl)propyl]-3-piperidinyl]karbonyl]amino]-3-pyridinpropanové kyseliny a derivátů - Google Patents
Způsob přípravy [S-(R*,S*)]-beta-[[[1-[1-oxo-3-(4-piperidinyl)propyl]-3-piperidinyl]karbonyl]amino]-3-pyridinpropanové kyseliny a derivátů Download PDFInfo
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- CZ20013431A3 CZ20013431A3 CZ20013431A CZ20013431A CZ20013431A3 CZ 20013431 A3 CZ20013431 A3 CZ 20013431A3 CZ 20013431 A CZ20013431 A CZ 20013431A CZ 20013431 A CZ20013431 A CZ 20013431A CZ 20013431 A3 CZ20013431 A3 CZ 20013431A3
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- hydrogen
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 title description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 57
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 13
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 159000000007 calcium salts Chemical class 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 239000007789 gas Substances 0.000 claims description 5
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 4
- 239000000920 calcium hydroxide Substances 0.000 claims description 4
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 150000003892 tartrate salts Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
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- 150000001735 carboxylic acids Chemical class 0.000 claims 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 27
- 239000000725 suspension Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
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- -1 N-tert-butoxycarbonylamino protecting group Chemical group 0.000 description 16
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- RFNSXSSACWHHMN-UHFFFAOYSA-N 4-benzyl-1,2-dihydrotriazol-5-one Chemical compound N1N=NC(CC=2C=CC=CC=2)=C1O RFNSXSSACWHHMN-UHFFFAOYSA-N 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- PPJXIHLNYDVTDI-UHFFFAOYSA-N dicloralurea Chemical compound ClC(Cl)(Cl)C(O)NC(=O)NC(O)C(Cl)(Cl)Cl PPJXIHLNYDVTDI-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
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- 239000000706 filtrate Substances 0.000 description 7
- ZKNMRQGIUVHOPC-UHFFFAOYSA-N methyl 3-amino-3-pyridin-3-ylprop-2-enoate Chemical compound COC(=O)C=C(N)C1=CC=CN=C1 ZKNMRQGIUVHOPC-UHFFFAOYSA-N 0.000 description 7
- YUMZDGVPZDQIMU-UHFFFAOYSA-N (3-methoxy-3-oxo-1-pyridin-1-ium-3-ylpropyl)azanium;dichloride Chemical compound Cl.Cl.COC(=O)CC(N)C1=CC=CN=C1 YUMZDGVPZDQIMU-UHFFFAOYSA-N 0.000 description 6
- HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- YUMZDGVPZDQIMU-JZGIKJSDSA-N [(1s)-3-methoxy-3-oxo-1-pyridin-1-ium-3-ylpropyl]azanium;dichloride Chemical compound Cl.Cl.COC(=O)C[C@H](N)C1=CC=CN=C1 YUMZDGVPZDQIMU-JZGIKJSDSA-N 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000010948 rhodium Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- AUYQMCCWFNSFGV-UHFFFAOYSA-N 3-piperidin-1-ium-4-ylpropanoate Chemical compound OC(=O)CCC1CCNCC1 AUYQMCCWFNSFGV-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
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- 238000004821 distillation Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000003495 polar organic solvent Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
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- 239000011780 sodium chloride Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- KBALQYDNPSCNJX-LJQANCHMSA-N (3r)-1-[3-(1-phenylmethoxycarbonylpiperidin-4-yl)propanoyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1C(=O)CCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 KBALQYDNPSCNJX-LJQANCHMSA-N 0.000 description 2
- SSAYTINUCCRGDR-OWOJBTEDSA-N (e)-3-pyridin-4-ylprop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=NC=C1 SSAYTINUCCRGDR-OWOJBTEDSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- FWBZEOPNLLITGS-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;piperidine-3-carboxylic acid Chemical compound OC(=O)C1CCCNC1.OC(=O)C(O)C(O)C(O)=O FWBZEOPNLLITGS-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 2
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- 230000002378 acidificating effect Effects 0.000 description 2
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- GUPPESBEIQALOS-UHFFFAOYSA-L calcium tartrate Chemical compound [Ca+2].[O-]C(=O)C(O)C(O)C([O-])=O GUPPESBEIQALOS-UHFFFAOYSA-L 0.000 description 2
- 239000001427 calcium tartrate Substances 0.000 description 2
- 235000011035 calcium tartrate Nutrition 0.000 description 2
- SIBMIRCAEJQCLN-UHFFFAOYSA-L calcium;3-(1-phenylmethoxycarbonylpiperidin-4-yl)propanoate Chemical compound [Ca+2].C1CC(CCC(=O)[O-])CCN1C(=O)OCC1=CC=CC=C1.C1CC(CCC(=O)[O-])CCN1C(=O)OCC1=CC=CC=C1 SIBMIRCAEJQCLN-UHFFFAOYSA-L 0.000 description 2
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- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
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- 239000006260 foam Substances 0.000 description 2
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
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- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
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- HHPGQKZOPPDLNH-NWAAXCJESA-N (2r,3r)-2,3-dihydroxybutanedioic acid;ethyl (3r)-piperidine-3-carboxylate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CCOC(=O)[C@@H]1CCCNC1 HHPGQKZOPPDLNH-NWAAXCJESA-N 0.000 description 1
- HHPGQKZOPPDLNH-OGFXRTJISA-N 2,3-dihydroxybutanedioic acid;ethyl (3r)-piperidine-3-carboxylate Chemical compound OC(=O)C(O)C(O)C(O)=O.CCOC(=O)[C@@H]1CCCNC1 HHPGQKZOPPDLNH-OGFXRTJISA-N 0.000 description 1
- NZTJJLCAFTZAGK-UHFFFAOYSA-N 3-(1-phenylmethoxycarbonylpiperidin-4-yl)propanoic acid Chemical compound C1CC(CCC(=O)O)CCN1C(=O)OCC1=CC=CC=C1 NZTJJLCAFTZAGK-UHFFFAOYSA-N 0.000 description 1
- QAJPWSCDQZUHIJ-UHFFFAOYSA-N 3-(piperidine-3-carbonylamino)propanoic acid Chemical class OC(=O)CCNC(=O)C1CCCNC1 QAJPWSCDQZUHIJ-UHFFFAOYSA-N 0.000 description 1
- XWZDPNBLQJCKNC-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CCC(O)=O)CC1 XWZDPNBLQJCKNC-UHFFFAOYSA-N 0.000 description 1
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- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical class [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
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- 238000002441 X-ray diffraction Methods 0.000 description 1
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- 229910052783 alkali metal Inorganic materials 0.000 description 1
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- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
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- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- XIWBSOUNZWSFKU-SSDOTTSWSA-N ethyl (3r)-piperidine-3-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCNC1 XIWBSOUNZWSFKU-SSDOTTSWSA-N 0.000 description 1
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JUQKVXRLRKKRPL-UHFFFAOYSA-N methyl 3-oxo-3-pyridin-3-ylpropanoate Chemical compound COC(=O)CC(=O)C1=CC=CN=C1 JUQKVXRLRKKRPL-UHFFFAOYSA-N 0.000 description 1
- DPQKNGIPZLINNJ-UHFFFAOYSA-N methyl 3-oxo-3-pyridin-3-ylpropanoate;dihydrochloride Chemical compound Cl.Cl.COC(=O)CC(=O)C1=CC=CN=C1 DPQKNGIPZLINNJ-UHFFFAOYSA-N 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12567199P | 1999-03-22 | 1999-03-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20013431A3 true CZ20013431A3 (cs) | 2003-04-16 |
Family
ID=22420863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20013431A CZ20013431A3 (cs) | 1999-03-22 | 2000-03-21 | Způsob přípravy [S-(R*,S*)]-beta-[[[1-[1-oxo-3-(4-piperidinyl)propyl]-3-piperidinyl]karbonyl]amino]-3-pyridinpropanové kyseliny a derivátů |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US6515130B1 (enExample) |
| EP (1) | EP1165543B1 (enExample) |
| JP (1) | JP2002540108A (enExample) |
| KR (1) | KR20020019895A (enExample) |
| CN (1) | CN1351600A (enExample) |
| AT (1) | ATE242235T1 (enExample) |
| AU (1) | AU775413B2 (enExample) |
| BR (1) | BR0010652A (enExample) |
| CA (1) | CA2368024A1 (enExample) |
| CZ (1) | CZ20013431A3 (enExample) |
| DE (1) | DE60003169T2 (enExample) |
| DK (1) | DK1165543T3 (enExample) |
| ES (1) | ES2199805T3 (enExample) |
| HK (1) | HK1046272A1 (enExample) |
| HR (1) | HRP20010767A2 (enExample) |
| HU (1) | HUP0201262A3 (enExample) |
| MX (1) | MXPA01009615A (enExample) |
| PT (1) | PT1165543E (enExample) |
| SK (1) | SK13562001A3 (enExample) |
| UA (1) | UA67832C2 (enExample) |
| WO (1) | WO2000056730A1 (enExample) |
| YU (1) | YU74601A (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0201263A3 (en) | 1999-03-22 | 2003-05-28 | Ortho Mcneil Pharm Inc | Synthesis of 3-amino-3-aryl propanoates and intermediates |
| NZ531243A (en) * | 2001-09-21 | 2006-08-31 | Sanofi Aventis | Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-A]pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-A]pyrimidin-5(1H)one derivatives |
| EP2744802B1 (en) | 2011-08-17 | 2017-01-04 | Piramal Imaging SA | Compounds for binding to the platelet specific glycoprotein iib/iiia and their use for imaging of thrombi |
| WO2014124943A1 (en) | 2013-02-12 | 2014-08-21 | Bayer Pharma Aktiengesellschaft | Metal chelate compounds for binding to the platelet specific glycoprotein iib/iiia |
| EP4289819A3 (en) | 2013-02-20 | 2024-01-10 | Reuter Chemische Apparatebau e.K. | Process for the preparation of enantiomerically enriched 3-aminopiperidine |
| WO2014173855A1 (en) | 2013-04-22 | 2014-10-30 | Reuter Chemische Apparatebau Kg | Process for preparing enantiomerically enriched 3-hydroxymethylpiperidine |
| KR102548998B1 (ko) | 2020-03-31 | 2023-06-29 | 재단법인 아산사회복지재단 | 혈전영상을 위한 방사성의약품 및 조성물 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE58243B1 (en) | 1983-12-07 | 1993-08-11 | Lonza Ag | A process for the preparation of optically-active 3-amino carboxylic acids |
| US5254573A (en) | 1991-10-15 | 1993-10-19 | Monsanto Company | Substituted heterocyclic derivatives useful as platelet aggregation inhibitors |
| CN1041919C (zh) * | 1993-09-22 | 1999-02-03 | 藤泽药品工业株式会社 | 用作血小板激活因子拮抗物的N-(3-哌啶基碳酰)-β-氨基丙酸衍生物 |
| US5770575A (en) * | 1994-03-16 | 1998-06-23 | Ortho Pharmaceutical Corporation | Nipecotic acid derivatives as antithrombotic compounds |
| CA2248809A1 (en) * | 1996-03-13 | 1997-09-18 | Fujisawa Pharmaceutical Co., Ltd. | N-[(r)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(s)-acetylamino-beta-alanine as fibrinogen receptor antagonist |
| DE69739239D1 (de) * | 1996-05-01 | 2009-03-19 | Ortho Mcneil Pharm Inc | Carboxamidderivate von Pyrrolidin, Piperidin und Hexahydropiperizin für Behandlung von Thrombosen |
| ES2167758T3 (es) | 1996-07-12 | 2002-05-16 | Searle & Co | Sintesis asimetrica de beta-aminoacidos quirales. |
| US6066651A (en) * | 1997-10-29 | 2000-05-23 | Ortho-Mcneil Pharmaceutical, Inc. | Orally-active nipecotamide glycolamide esters for the treatment of thrombosis disorders |
-
2000
- 2000-03-21 ES ES00916573T patent/ES2199805T3/es not_active Expired - Lifetime
- 2000-03-21 EP EP00916573A patent/EP1165543B1/en not_active Expired - Lifetime
- 2000-03-21 CA CA002368024A patent/CA2368024A1/en not_active Abandoned
- 2000-03-21 JP JP2000606591A patent/JP2002540108A/ja active Pending
- 2000-03-21 DK DK00916573T patent/DK1165543T3/da active
- 2000-03-21 HU HU0201262A patent/HUP0201262A3/hu unknown
- 2000-03-21 US US09/532,375 patent/US6515130B1/en not_active Expired - Lifetime
- 2000-03-21 CZ CZ20013431A patent/CZ20013431A3/cs unknown
- 2000-03-21 YU YU74601A patent/YU74601A/sh unknown
- 2000-03-21 MX MXPA01009615A patent/MXPA01009615A/es unknown
- 2000-03-21 BR BR0010652-6A patent/BR0010652A/pt not_active IP Right Cessation
- 2000-03-21 WO PCT/US2000/007462 patent/WO2000056730A1/en not_active Ceased
- 2000-03-21 HR HR20010767A patent/HRP20010767A2/hr not_active Application Discontinuation
- 2000-03-21 CN CN00807617A patent/CN1351600A/zh active Pending
- 2000-03-21 DE DE60003169T patent/DE60003169T2/de not_active Expired - Fee Related
- 2000-03-21 AT AT00916573T patent/ATE242235T1/de not_active IP Right Cessation
- 2000-03-21 KR KR1020017012100A patent/KR20020019895A/ko not_active Withdrawn
- 2000-03-21 AU AU37661/00A patent/AU775413B2/en not_active Ceased
- 2000-03-21 UA UA2001096538A patent/UA67832C2/uk unknown
- 2000-03-21 PT PT00916573T patent/PT1165543E/pt unknown
- 2000-03-21 SK SK1356-2001A patent/SK13562001A3/sk unknown
- 2000-03-21 HK HK02107463.1A patent/HK1046272A1/zh unknown
-
2002
- 2002-02-22 US US10/081,289 patent/US20020137937A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BR0010652A (pt) | 2002-07-16 |
| HRP20010767A2 (en) | 2002-12-31 |
| SK13562001A3 (sk) | 2002-08-06 |
| DE60003169T2 (de) | 2005-10-27 |
| CN1351600A (zh) | 2002-05-29 |
| KR20020019895A (ko) | 2002-03-13 |
| DK1165543T3 (da) | 2003-09-29 |
| CA2368024A1 (en) | 2000-09-28 |
| JP2002540108A (ja) | 2002-11-26 |
| ATE242235T1 (de) | 2003-06-15 |
| AU775413B2 (en) | 2004-07-29 |
| DE60003169D1 (de) | 2003-07-10 |
| US20020137937A1 (en) | 2002-09-26 |
| EP1165543A1 (en) | 2002-01-02 |
| UA67832C2 (uk) | 2004-07-15 |
| WO2000056730A1 (en) | 2000-09-28 |
| MXPA01009615A (es) | 2003-07-21 |
| PT1165543E (pt) | 2003-10-31 |
| EP1165543B1 (en) | 2003-06-04 |
| YU74601A (sh) | 2004-05-12 |
| US6515130B1 (en) | 2003-02-04 |
| HU0201262D0 (enExample) | 2002-05-29 |
| HUP0201262A3 (en) | 2003-12-29 |
| HK1046272A1 (zh) | 2003-01-03 |
| ES2199805T3 (es) | 2004-03-01 |
| AU3766100A (en) | 2000-10-09 |
| HUP0201262A2 (en) | 2002-08-28 |
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