FI97133B - Förfarande för framställning av optiskt aktiva 2-oxoimidazolidinderivat - Google Patents
Förfarande för framställning av optiskt aktiva 2-oxoimidazolidinderivat Download PDFInfo
- Publication number
- FI97133B FI97133B FI895795A FI895795A FI97133B FI 97133 B FI97133 B FI 97133B FI 895795 A FI895795 A FI 895795A FI 895795 A FI895795 A FI 895795A FI 97133 B FI97133 B FI 97133B
- Authority
- FI
- Finland
- Prior art keywords
- compound
- oxoimidazolidine
- configuration
- group
- following formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical class O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- -1 propionic acid compound Chemical class 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- 238000006482 condensation reaction Methods 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 239000006188 syrup Substances 0.000 claims description 5
- 235000020357 syrup Nutrition 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- KZKRPYCBSZIQKN-UHFFFAOYSA-N 2-Imidazolidone-4-carboxylic acid Chemical compound OC(=O)C1CNC(=O)N1 KZKRPYCBSZIQKN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 150000002688 maleic acid derivatives Chemical class 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 1
- VFAVNRVDTAPBNR-UBHSHLNASA-N imidaprilat Chemical compound C([C@H](N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)C(O)=O)CC1=CC=CC=C1 VFAVNRVDTAPBNR-UBHSHLNASA-N 0.000 claims 1
- 230000001766 physiological effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229930182843 D-Lactic acid Natural products 0.000 description 5
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 5
- 229940022769 d- lactic acid Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- MONMFXREYOKQTI-UHFFFAOYSA-N 2-bromopropanoic acid Chemical compound CC(Br)C(O)=O MONMFXREYOKQTI-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- SXTMXSXWPZPIFG-JTQLQIEISA-N benzyl (4s)-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound N1C(=O)N(C)C[C@H]1C(=O)OCC1=CC=CC=C1 SXTMXSXWPZPIFG-JTQLQIEISA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- WFLQXECQLHZKMV-NSHDSACASA-N ethyl (2s)-2-amino-4-phenylbutanoate Chemical compound CCOC(=O)[C@@H](N)CCC1=CC=CC=C1 WFLQXECQLHZKMV-NSHDSACASA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- JHSLVEQWBDYFQN-LURJTMIESA-N tert-butyl (4s)-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound CN1C[C@@H](C(=O)OC(C)(C)C)NC1=O JHSLVEQWBDYFQN-LURJTMIESA-N 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QXYOROBKCZWFKK-MRVPVSSYSA-N (2r)-2-(4-methylphenyl)sulfonyloxypropanoic acid Chemical compound OC(=O)[C@@H](C)OS(=O)(=O)C1=CC=C(C)C=C1 QXYOROBKCZWFKK-MRVPVSSYSA-N 0.000 description 1
- LFMBKSRGQHUJKP-GSVOUGTGSA-N (2r)-2-methylsulfonyloxypropanoic acid Chemical compound OC(=O)[C@@H](C)OS(C)(=O)=O LFMBKSRGQHUJKP-GSVOUGTGSA-N 0.000 description 1
- AEDVCQIVTIIFMO-VKHMYHEASA-N (4s)-1-methyl-2-oxoimidazolidine-4-carboxylic acid Chemical compound CN1C[C@@H](C(O)=O)NC1=O AEDVCQIVTIIFMO-VKHMYHEASA-N 0.000 description 1
- SMHIZTOYZYYLCU-AKGZTFGVSA-N (4s)-3-(2-bromopropanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid Chemical compound CC(Br)C(=O)N1[C@H](C(O)=O)CN(C)C1=O SMHIZTOYZYYLCU-AKGZTFGVSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- OZGMODDEIHYPRY-UHFFFAOYSA-N 2-bromopropanoyl chloride Chemical compound CC(Br)C(Cl)=O OZGMODDEIHYPRY-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-M 4-phenylbutyrate Chemical compound [O-]C(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-M 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 101100328518 Caenorhabditis elegans cnt-1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- LSLQGMMMRMDXHN-GEUPQXMHSA-N Imidapril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 LSLQGMMMRMDXHN-GEUPQXMHSA-N 0.000 description 1
- JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- VYEIIPLQOBKTAZ-INIZCTEOSA-N benzyl (2s)-2-amino-4-phenylbutanoate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 VYEIIPLQOBKTAZ-INIZCTEOSA-N 0.000 description 1
- MYLWJZSZWFAULT-APWZRJJASA-N benzyl (4s)-1-methyl-3-[(2r)-2-(4-methylphenyl)sulfonyloxypropanoyl]-2-oxoimidazolidine-4-carboxylate Chemical compound O([C@H](C)C(=O)N1C(N(C)C[C@H]1C(=O)OCC=1C=CC=CC=1)=O)S(=O)(=O)C1=CC=C(C)C=C1 MYLWJZSZWFAULT-APWZRJJASA-N 0.000 description 1
- GVDNSSMZVYGUMQ-YPMHNXCESA-N benzyl (4s)-1-methyl-3-[(2r)-2-methylsulfonyloxypropanoyl]-2-oxoimidazolidine-4-carboxylate Chemical compound C1N(C)C(=O)N(C(=O)[C@H](OS(C)(=O)=O)C)[C@@H]1C(=O)OCC1=CC=CC=C1 GVDNSSMZVYGUMQ-YPMHNXCESA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PTFKZMFFSIYCOV-MERQFXBCSA-N ethyl (2s)-2-amino-4-phenylbutanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CCC1=CC=CC=C1 PTFKZMFFSIYCOV-MERQFXBCSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N gamma-phenylbutyric acid Natural products OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- JSROFURYAHZGNA-OYDLWJJNSA-N tert-butyl (4s)-1-methyl-2-oxo-3-[(2s)-2-[[(2s)-1-oxo-4-phenyl-1-phenylmethoxybutan-2-yl]amino]propanoyl]imidazolidine-4-carboxylate Chemical compound C([C@H](N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(=O)OC(C)(C)C)=O)C(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 JSROFURYAHZGNA-OYDLWJJNSA-N 0.000 description 1
- PNFSPJGLVSAITF-HIFRSBDPSA-N tert-butyl (4s)-1-methyl-3-[(2r)-2-(4-methylphenyl)sulfonyloxypropanoyl]-2-oxoimidazolidine-4-carboxylate Chemical compound O([C@H](C)C(=O)N1C(N(C)C[C@H]1C(=O)OC(C)(C)C)=O)S(=O)(=O)C1=CC=C(C)C=C1 PNFSPJGLVSAITF-HIFRSBDPSA-N 0.000 description 1
- YCHKNKZKPFFKEV-WDSOQIARSA-N tert-butyl (4s)-3-[(2s)-2-[[(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-1-methyl-2-oxoimidazolidine-4-carboxylate Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(=O)OC(C)(C)C)=O)CC1=CC=CC=C1 YCHKNKZKPFFKEV-WDSOQIARSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole 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
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
- C07D233/38—One oxygen atom with acyl radicals or hetero atoms directly attached to ring nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (10)
1. Förfarande för framställning av ett optiskt aktivt 2-oxoimi-dazolidinderivat enligt formeln: CH3—N-1 A AS) O N COOH >C\(S) (S) . O CH—UH—CH—COOR 'v· I 1 Γλ ch3 ch2ch2—^ y r · · • · · IM • · » 4 · · * I I • t * P · · I t I väri R1 är en väteatom eller en lägre alkylgrupp, ! * * · · * , kännetecknat av att ett 2-oxoimidazolidin-4-karbo-·.: xylsyraesterderivat, som har (S)-konfiguration enligt formeln: 19 97133 CHj—N-1 λ Λ3’ , (f N' Ν COOR H väri R2 är en tert.butylgrupp eller en benzylgrupp, fär reagera med ett reaktivt derivat i en propionsyraförenings karboxylgrupp, som har (R) konfiguration enligt formeln: (R) , HOOC—CH—0S02R <ii][> ch3 väri R3 är en lägre alkylgrupp eller en arylgrupp; varvid bildas ett 3-acyl-2-oxoimidazolidin-4-karboxylsyraester-derivat, som har (S,R)-konfiguration enligt formeln: CH3—N-1 A As> 2 <iv> O Nx x COOR ς/ ^CH—0S02R3 ch3 • « • · « • · väri R2 och R3 innebär samma som definierats ovan, « · • · » • · • · · *·*·’ och genom att Iita ifrägavarande förening (IV) reagera med en aminosyraester, som har (S)-konfiguration enligt formeln: • · · • · « • · · r : : (S) H2N—CH—COOR (V) . ch2ch2-^~^ : väri R4 är en lägre alkylgrupp eller en benzylgrupp, 20 9 7 1 33 varvid bildas ett 2-oxoimidazolidindiesterderivat, som har (S,S,S)-konfiguration enligt följande formel: CH3—N-1 J\ y\S) 2 <vi> 'n' ' COOR /C\(S) <S) o CH—NH—CH—COOR 1 1 /“\ ch3 ch2ch2—6 y vari RJ och R4 innebär samma som definierats ovan, och därefter elimineras R2 frAn sagda förening och dA R4 är en benzylgrupp, elimineras därtill även denna benzylgrupp.
2. Förfarande enligt krav 1, kännetecknat av att R3 i nämnda förening (III) är en metylgrupp, etylgrupp, fenylgrupp eller p-metylfenylgrupp.
3. Förfarande enligt patentkrav 1, kännetecknat av att det reaktiva derivatet i föreningens (III) karboxylgrupp Mr en aktiv ester med N-hydroxisuccinimid, en syraklorid eller en syrabromid.
4. Förfarande enligt patentkrav 1, kännetecknat av :*·β> att föreningens (II) kondenseringsreaktion med föreningen (III) : .·. utförs i närvaro av en syraacceptor, som är vald frAn kalium-t-• ♦ · butoxid, natriumhydroxid eller kaliumhydroxid. 1
♦ · • · • ♦ · • * 5. Förfarande enligt patentkrav 1, kännetecknat av att föreningens (II) kondenseringsreaktion med föreningen (III) utförs i närvaro av ett lösningsmedel, som är valt frAn tetra- «·* v · hydrofuran, dioxan eller dimetylformamid.
···. 6. Förfarande enligt patentkrav 1, kännetecknat av att föreningens (II) kondenseringsreaktion med föreningen (III) : utförs mellan kylning och rumstemperatur. «a i 1:111 |.| Irt 21 97133
7. Förfarande enligt patentkrav 1, kännetecknat av att föreningens (IV) kondenseringsreaktion med föreningen (V) utförs i närvaro av en syraacceptor, som är vald frän kaliumkar-bonat, natriumkarbonat, trietylamin, tributylamin eller N-metyl-morfolin.
8. Förfarande enligt patentkrav 1, kännetecknat av att föreningens (IV) kondenseringsreaktion med föreningen (V) utförs i närvaro av ett lösningsmedel, som är valt frlin dimetyl-sulfoxid, hexametylfosforylamid eller dimetylformamid.
9. Förfarande enligt patentkrav 1, kännetecknat av att föreningens (IV) kondenseringsreaktion med föreningen (V) utförs mellan rumstemperatur och upphettningstemperatur.
10. Ett 3-acyl-2-oxoimidazolidin-4-karboxylsyraesterderivat enligt följande formel, som har (S,R)-konfiguration, 0^\N/nCOOR2 'yc\(R) . o CH—0S02R ch3 väri R2 är en tert.butylgrupp eller en benzylgrupp, och R3 är en - ·' lägre alkylgrupp eller en arylgrupp. 9 · · 9 · t(< 9 1» 1 • 9 « • 1 1 t • · • · < # » I « · · i : *»1 · ·
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31874588 | 1988-12-16 | ||
| JP63318745A JPH0645603B2 (ja) | 1988-12-16 | 1988-12-16 | 光学活性２‐オキソイミダゾリジン誘導体の製法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI895795A0 FI895795A0 (sv) | 1989-12-04 |
| FI97133B true FI97133B (sv) | 1996-07-15 |
| FI97133C FI97133C (sv) | 1996-10-25 |
Family
ID=18102470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI895795A FI97133C (sv) | 1988-12-16 | 1989-12-04 | Förfarande för framställning av optiskt aktiva 2-oxoimidazolidinderivat |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5013845A (sv) |
| EP (1) | EP0373881B1 (sv) |
| JP (1) | JPH0645603B2 (sv) |
| KR (1) | KR950009364B1 (sv) |
| CN (1) | CN1032308C (sv) |
| AT (1) | ATE100817T1 (sv) |
| AU (1) | AU622959B2 (sv) |
| CA (1) | CA2004606C (sv) |
| DE (1) | DE68912745T2 (sv) |
| DK (1) | DK174701B1 (sv) |
| ES (1) | ES2062044T3 (sv) |
| FI (1) | FI97133C (sv) |
| HK (1) | HK34195A (sv) |
| HU (1) | HU203730B (sv) |
| IE (1) | IE64315B1 (sv) |
| IL (1) | IL92456A0 (sv) |
| SG (1) | SG4795G (sv) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104513292A (zh) * | 2013-09-29 | 2015-04-15 | 山东新时代药业有限公司 | 一种雷米普利的制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5788165A (en) * | 1980-11-21 | 1982-06-01 | Tanabe Seiyaku Co Ltd | 2-oxoimidazolidine-4-carboxylic acid derivative and its preparation |
| JPS6058233B2 (ja) * | 1982-05-24 | 1985-12-19 | 田辺製薬株式会社 | ２−オキソイミダゾリジン誘導体及びその製法 |
| JPS6058233A (ja) * | 1983-08-11 | 1985-04-04 | ザ・アプジヨン・カンパニー | 滅菌懸濁液及び溶液の保持及び混合装置 |
-
1988
- 1988-12-16 JP JP63318745A patent/JPH0645603B2/ja not_active Expired - Lifetime
-
1989
- 1989-11-27 IL IL92456A patent/IL92456A0/xx unknown
- 1989-12-04 US US07/445,060 patent/US5013845A/en not_active Expired - Lifetime
- 1989-12-04 FI FI895795A patent/FI97133C/sv active IP Right Grant
- 1989-12-05 CN CN89109175A patent/CN1032308C/zh not_active Expired - Lifetime
- 1989-12-05 CA CA002004606A patent/CA2004606C/en not_active Expired - Lifetime
- 1989-12-12 AU AU46195/89A patent/AU622959B2/en not_active Expired
- 1989-12-12 ES ES89312965T patent/ES2062044T3/es not_active Expired - Lifetime
- 1989-12-12 EP EP89312965A patent/EP0373881B1/en not_active Expired - Lifetime
- 1989-12-12 DE DE89312965T patent/DE68912745T2/de not_active Expired - Lifetime
- 1989-12-12 AT AT89312965T patent/ATE100817T1/de not_active IP Right Cessation
- 1989-12-14 IE IE400489A patent/IE64315B1/en not_active IP Right Cessation
- 1989-12-15 KR KR1019890018658A patent/KR950009364B1/ko not_active IP Right Cessation
- 1989-12-15 HU HU896640A patent/HU203730B/hu unknown
- 1989-12-15 DK DK198906382A patent/DK174701B1/da not_active IP Right Cessation
-
1995
- 1995-01-13 SG SG4795A patent/SG4795G/en unknown
- 1995-03-09 HK HK34195A patent/HK34195A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1032308C (zh) | 1996-07-17 |
| SG4795G (en) | 1995-06-16 |
| JPH02164869A (ja) | 1990-06-25 |
| AU4619589A (en) | 1990-06-21 |
| CN1043705A (zh) | 1990-07-11 |
| HU896640D0 (en) | 1990-02-28 |
| DK638289A (da) | 1990-06-17 |
| US5013845A (en) | 1991-05-07 |
| ATE100817T1 (de) | 1994-02-15 |
| AU622959B2 (en) | 1992-04-30 |
| JPH0645603B2 (ja) | 1994-06-15 |
| FI895795A0 (sv) | 1989-12-04 |
| DE68912745T2 (de) | 1994-05-11 |
| KR950009364B1 (ko) | 1995-08-21 |
| DK638289D0 (da) | 1989-12-15 |
| KR900009603A (ko) | 1990-07-05 |
| HU203730B (en) | 1991-09-30 |
| ES2062044T3 (es) | 1994-12-16 |
| IL92456A0 (en) | 1990-08-31 |
| DE68912745D1 (de) | 1994-03-10 |
| EP0373881A2 (en) | 1990-06-20 |
| DK174701B1 (da) | 2003-09-29 |
| CA2004606C (en) | 1997-01-07 |
| EP0373881A3 (en) | 1990-08-16 |
| EP0373881B1 (en) | 1994-01-26 |
| CA2004606A1 (en) | 1990-06-16 |
| IE64315B1 (en) | 1995-07-26 |
| HK34195A (en) | 1995-03-17 |
| HUT52064A (en) | 1990-06-28 |
| FI97133C (sv) | 1996-10-25 |
| IE894004L (en) | 1990-06-16 |
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Owner name: TANABE SEIYAKU CO., LTD |
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| FG | Patent granted |
Owner name: TANABE SEIYAKU CO., . LTD. |