JP2014530831A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2014530831A5 JP2014530831A5 JP2014536208A JP2014536208A JP2014530831A5 JP 2014530831 A5 JP2014530831 A5 JP 2014530831A5 JP 2014536208 A JP2014536208 A JP 2014536208A JP 2014536208 A JP2014536208 A JP 2014536208A JP 2014530831 A5 JP2014530831 A5 JP 2014530831A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- phenyl
- methyl
- isoxazol
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 73
- 238000000034 method Methods 0.000 claims 52
- 239000002904 solvent Substances 0.000 claims 35
- 238000006243 chemical reaction Methods 0.000 claims 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 12
- 239000002585 base Substances 0.000 claims 12
- 108090000790 Enzymes Proteins 0.000 claims 11
- 102000004190 Enzymes Human genes 0.000 claims 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 11
- 239000011942 biocatalyst Substances 0.000 claims 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 9
- 238000004904 shortening Methods 0.000 claims 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 6
- 239000002253 acid Substances 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 230000002210 biocatalytic effect Effects 0.000 claims 4
- 125000001188 haloalkyl group Chemical group 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- -1 hydroxypropyl Chemical group 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 239000000725 suspension Substances 0.000 claims 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 3
- KTZGIWHJTOGZRQ-UHFFFAOYSA-N 6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carbonitrile Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC1=CC=C(C#N)C=N1 KTZGIWHJTOGZRQ-UHFFFAOYSA-N 0.000 claims 3
- DBPRZHYSXRZSHX-UHFFFAOYSA-N 6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxylic acid Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC1=CC=C(C(O)=O)C=N1 DBPRZHYSXRZSHX-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 238000001914 filtration Methods 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 claims 2
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 2
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 claims 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims 2
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 claims 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- SYTGZUMODGDAOP-UHFFFAOYSA-N 6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-(2,2,2-trifluoroethyl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC1=CC=C(C(=O)NCC(F)(F)F)C=N1 SYTGZUMODGDAOP-UHFFFAOYSA-N 0.000 claims 2
- RKAXYUZQFLSKQW-UHFFFAOYSA-N 6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-(oxan-4-yl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)NC1CCOCC1 RKAXYUZQFLSKQW-UHFFFAOYSA-N 0.000 claims 2
- SMSDGZOOYOAPBR-UHFFFAOYSA-N 6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-propan-2-ylpyridine-3-carboxamide Chemical compound N1=CC(C(=O)NC(C)C)=CC=C1OCC1=C(C)ON=C1C1=CC=C(F)C=C1 SMSDGZOOYOAPBR-UHFFFAOYSA-N 0.000 claims 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 claims 2
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 claims 2
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 claims 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 claims 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 2
- ZBSKQMBBDAMUGZ-UHFFFAOYSA-N [6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]-morpholin-4-ylmethanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCOCC1 ZBSKQMBBDAMUGZ-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 239000012062 aqueous buffer Substances 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 2
- 238000004090 dissolution Methods 0.000 claims 2
- 238000001035 drying Methods 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000012535 impurity Substances 0.000 claims 2
- 238000002955 isolation Methods 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims 2
- TVGGDSDCPKZAMT-UHFFFAOYSA-N n-(cyclopropylmethyl)-6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)NCC1CC1 TVGGDSDCPKZAMT-UHFFFAOYSA-N 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 239000002953 phosphate buffered saline Substances 0.000 claims 2
- 239000011541 reaction mixture Substances 0.000 claims 2
- 239000012312 sodium hydride Substances 0.000 claims 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 2
- 238000005406 washing Methods 0.000 claims 2
- WIIOERFDLLICCO-UHFFFAOYSA-N (4-hydroxypiperidin-1-yl)-[6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCC(O)CC1 WIIOERFDLLICCO-UHFFFAOYSA-N 0.000 claims 1
- UOMTVKMKHZMFMQ-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide;hydrochloride Chemical compound Cl.O=S1(=O)CCNCC1 UOMTVKMKHZMFMQ-UHFFFAOYSA-N 0.000 claims 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 claims 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims 1
- MZYXACXBSSTJLY-UHFFFAOYSA-N 6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl-[6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]pyridin-3-yl]methanone Chemical compound C=1C=C(C(=O)N2CC3=NN=CN3CC2)C=NC=1OCC1=C(C)ON=C1C1=CC=CC=C1 MZYXACXBSSTJLY-UHFFFAOYSA-N 0.000 claims 1
- MHKSCGLYAXDKGL-UHFFFAOYSA-N 6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]-n-(1-methylpyrazol-4-yl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC(N=C1)=CC=C1C(=O)NC=1C=NN(C)C=1 MHKSCGLYAXDKGL-UHFFFAOYSA-N 0.000 claims 1
- ZRUCBARHGRYQAA-UHFFFAOYSA-N 6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]-n-(pyridin-2-ylmethyl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC(N=C1)=CC=C1C(=O)NCC1=CC=CC=N1 ZRUCBARHGRYQAA-UHFFFAOYSA-N 0.000 claims 1
- UFLGFAJSQNVAES-UHFFFAOYSA-N 6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]-n-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyridine-3-carboxamide Chemical compound O1N=C(C(C)C)C=C1CNC(=O)C(C=N1)=CC=C1OCC1=C(C)ON=C1C1=CC=CC=C1 UFLGFAJSQNVAES-UHFFFAOYSA-N 0.000 claims 1
- NEWJZWIATNUILR-UHFFFAOYSA-N 6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]pyridine-3-carboxylic acid Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC1=CC=C(C(O)=O)C=N1 NEWJZWIATNUILR-UHFFFAOYSA-N 0.000 claims 1
- OUDUXYNMAIENIK-UHFFFAOYSA-N 6-[[3-(3-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carbonitrile Chemical compound CC=1ON=C(C=2C=C(Cl)C=CC=2)C=1COC1=CC=C(C#N)C=N1 OUDUXYNMAIENIK-UHFFFAOYSA-N 0.000 claims 1
- NPKISILOCKEOTB-UHFFFAOYSA-N 6-[[3-(3-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxylic acid Chemical compound CC=1ON=C(C=2C=C(Cl)C=CC=2)C=1COC1=CC=C(C(O)=O)C=N1 NPKISILOCKEOTB-UHFFFAOYSA-N 0.000 claims 1
- VIFMHLABYKWPLL-UHFFFAOYSA-N 6-[[3-(3-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-(2,2,2-trifluoroethyl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1COC1=CC=C(C(=O)NCC(F)(F)F)C=N1 VIFMHLABYKWPLL-UHFFFAOYSA-N 0.000 claims 1
- QNECOKFREODBCI-UHFFFAOYSA-N 6-[[3-(3-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carbonitrile Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1COC1=CC=C(C#N)C=N1 QNECOKFREODBCI-UHFFFAOYSA-N 0.000 claims 1
- JMCQJTNDPXJODJ-UHFFFAOYSA-N 6-[[3-(3-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxylic acid Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1COC1=CC=C(C(O)=O)C=N1 JMCQJTNDPXJODJ-UHFFFAOYSA-N 0.000 claims 1
- FESJPTYXCWUOQM-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-1,2-oxazol-4-yl]methoxy]-n-(3-hydroxypropyl)pyridine-3-carboxamide Chemical compound N1=CC(C(=O)NCCCO)=CC=C1OCC1=CON=C1C1=CC=C(Cl)C=C1 FESJPTYXCWUOQM-UHFFFAOYSA-N 0.000 claims 1
- RSYYOIOLHPGIQZ-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-1,2-oxazol-4-yl]methoxy]-n-propan-2-ylpyridine-3-carboxamide Chemical compound N1=CC(C(=O)NC(C)C)=CC=C1OCC1=CON=C1C1=CC=C(Cl)C=C1 RSYYOIOLHPGIQZ-UHFFFAOYSA-N 0.000 claims 1
- JLMQXTAOTPLOQJ-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-1,2-oxazol-4-yl]methoxy]pyridine-3-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C1=NOC=C1COC1=CC=C(C#N)C=N1 JLMQXTAOTPLOQJ-UHFFFAOYSA-N 0.000 claims 1
- PHYDBFMOGNJSQD-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1OCC1=CON=C1C1=CC=C(Cl)C=C1 PHYDBFMOGNJSQD-UHFFFAOYSA-N 0.000 claims 1
- HDNWJKMMTZAYSO-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-(1-methylpyrazol-4-yl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC(Cl)=CC=2)C=1COC(N=C1)=CC=C1C(=O)NC=1C=NN(C)C=1 HDNWJKMMTZAYSO-UHFFFAOYSA-N 0.000 claims 1
- MBRABNLWKANAQU-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]-n-(cyclopropylmethyl)pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC(Cl)=CC=2)C=1COC(N=C1)=CC=C1C(=O)NCC1CC1 MBRABNLWKANAQU-UHFFFAOYSA-N 0.000 claims 1
- GSYQJUXQFDAEFC-UHFFFAOYSA-N 6-[[3-(4-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxylic acid Chemical compound CC=1ON=C(C=2C=CC(Cl)=CC=2)C=1COC1=CC=C(C(O)=O)C=N1 GSYQJUXQFDAEFC-UHFFFAOYSA-N 0.000 claims 1
- ORIQLMBUPMABDV-UHFFFAOYSA-N 6-chloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C=N1 ORIQLMBUPMABDV-UHFFFAOYSA-N 0.000 claims 1
- 241001489200 Fusarium poae Species 0.000 claims 1
- 239000007995 HEPES buffer Substances 0.000 claims 1
- 239000007993 MOPS buffer Substances 0.000 claims 1
- YNLCVAQJIKOXER-UHFFFAOYSA-N N-[tris(hydroxymethyl)methyl]-3-aminopropanesulfonic acid Chemical compound OCC(CO)(CO)NCCCS(O)(=O)=O YNLCVAQJIKOXER-UHFFFAOYSA-N 0.000 claims 1
- 108010033272 Nitrilase Proteins 0.000 claims 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 claims 1
- 239000012317 TBTU Substances 0.000 claims 1
- 239000007997 Tricine buffer Substances 0.000 claims 1
- 208000034953 Twin anemia-polycythemia sequence Diseases 0.000 claims 1
- YTPVTPNVCHCMAT-UHFFFAOYSA-N [3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methanol Chemical compound OCC1=C(C)ON=C1C1=CC=C(F)C=C1 YTPVTPNVCHCMAT-UHFFFAOYSA-N 0.000 claims 1
- QGDVBORCHDZMAL-UHFFFAOYSA-N [6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]pyridin-3-yl]-(1,3-thiazolidin-3-yl)methanone Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCSC1 QGDVBORCHDZMAL-UHFFFAOYSA-N 0.000 claims 1
- UDOWVKSGYVJYKH-UHFFFAOYSA-N [6-[[3-(3-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]-(1,1-dioxo-1,4-thiazinan-4-yl)methanone Chemical compound CC=1ON=C(C=2C=C(Cl)C=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 UDOWVKSGYVJYKH-UHFFFAOYSA-N 0.000 claims 1
- VSAFLTQPWBLZMR-UHFFFAOYSA-N [6-[[3-(3-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]-thiomorpholin-4-ylmethanone Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCSCC1 VSAFLTQPWBLZMR-UHFFFAOYSA-N 0.000 claims 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 239000007998 bicine buffer Substances 0.000 claims 1
- MAPRDOKILZKGDP-UHFFFAOYSA-N bromo-chloro-iodomethanesulfonic acid Chemical compound OS(=O)(=O)C(Cl)(Br)I MAPRDOKILZKGDP-UHFFFAOYSA-N 0.000 claims 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 claims 1
- VUSHQLWDOJFSGF-UHFFFAOYSA-L disodium 3-carboxy-3,5-dihydroxy-5-oxopentanoate chloride Chemical compound [Na+].[Na+].Cl.[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O VUSHQLWDOJFSGF-UHFFFAOYSA-L 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims 1
- 230000000813 microbial effect Effects 0.000 claims 1
- 244000005700 microbiome Species 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- YEUILAQZGLYAOV-UHFFFAOYSA-N n-(4-fluorophenyl)-6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1COC(N=C1)=CC=C1C(=O)NC1=CC=C(F)C=C1 YEUILAQZGLYAOV-UHFFFAOYSA-N 0.000 claims 1
- ZSIMYOZDODKNHZ-UHFFFAOYSA-N n-cyclopropyl-6-[[3-(3-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridine-3-carboxamide Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1COC(N=C1)=CC=C1C(=O)NC1CC1 ZSIMYOZDODKNHZ-UHFFFAOYSA-N 0.000 claims 1
- IBXUHBAAEUJVSO-UHFFFAOYSA-N n-methyl-6-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methoxy]-n-(oxan-4-yl)pyridine-3-carboxamide Chemical compound C=1C=C(OCC=2C(=NOC=2C)C=2C=CC=CC=2)N=CC=1C(=O)N(C)C1CCOCC1 IBXUHBAAEUJVSO-UHFFFAOYSA-N 0.000 claims 1
- 238000006386 neutralization reaction Methods 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 230000020477 pH reduction Effects 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 1
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11185992.2 | 2011-10-20 | ||
| EP11185992 | 2011-10-20 | ||
| PCT/EP2012/070521 WO2013057123A1 (en) | 2011-10-20 | 2012-10-17 | Process for the preparation of isoxazolyl-methoxy-nicotinic acids |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014530831A JP2014530831A (ja) | 2014-11-20 |
| JP2014530831A5 true JP2014530831A5 (https=) | 2015-11-05 |
| JP5923174B2 JP5923174B2 (ja) | 2016-05-24 |
Family
ID=47019026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014536208A Active JP5923174B2 (ja) | 2011-10-20 | 2012-10-17 | イソオキサゾリル−メトキシ−ニコチン酸の調製方法 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US8604062B2 (https=) |
| EP (1) | EP2768827B1 (https=) |
| JP (1) | JP5923174B2 (https=) |
| KR (2) | KR20140084209A (https=) |
| CN (1) | CN103889978B (https=) |
| AR (1) | AR088358A1 (https=) |
| AU (1) | AU2012321095B2 (https=) |
| BR (1) | BR112014009266B1 (https=) |
| CA (2) | CA3112072C (https=) |
| DK (1) | DK2768827T3 (https=) |
| ES (1) | ES2613802T3 (https=) |
| HU (1) | HUE031276T2 (https=) |
| IL (1) | IL231645A (https=) |
| MX (1) | MX2014004688A (https=) |
| MY (1) | MY164880A (https=) |
| PL (1) | PL2768827T3 (https=) |
| RU (1) | RU2014118966A (https=) |
| SG (1) | SG11201401626UA (https=) |
| SI (1) | SI2768827T1 (https=) |
| WO (1) | WO2013057123A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112020004116A2 (pt) * | 2017-08-28 | 2020-09-01 | University Of Maryland, Baltimore | novos moduladores do receptor de ácido gama aminobutírico tipo a para distúrbios de humor |
| IL279266B2 (en) | 2018-06-13 | 2024-03-01 | Hoffmann La Roche | New isoxazolyl ether derivatives as gaba a alpha5 pam |
| HU231223B1 (hu) | 2018-09-28 | 2022-01-28 | Richter Gedeon Nyrt. | GABAA A5 receptor modulátor hatású biciklusos vegyületek |
| EP4126858B1 (en) | 2020-03-26 | 2026-03-18 | Richter Gedeon Nyrt. | Dihydro-2-pyrrolo[3,4-c]pyridine derivatives as gabaa a5 receptor modulators |
| GB202013765D0 (en) * | 2020-09-02 | 2020-10-14 | Gw Res Ltd | Method of preparing cannabinoids |
| CN116854680A (zh) | 2022-03-28 | 2023-10-10 | 上海赛默罗生物科技有限公司 | 异噁唑-杂环类衍生物、药物组合物和用途 |
| CN119265168B (zh) * | 2024-11-05 | 2025-06-20 | 江南大学 | 一种新型腈水解酶及其在烟酸生物合成中的应用 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1102755B1 (en) | 1998-08-07 | 2006-01-04 | Chiron Corporation | Substituted isoxazole derivatives as estrogen receptor modulators |
| US6551804B2 (en) * | 1999-07-12 | 2003-04-22 | E. I. Du Pont De Nemours And Company | Process for preparing 4-cyanopentanoic acid |
| US20060148858A1 (en) | 2002-05-24 | 2006-07-06 | Tsuyoshi Maekawa | 1, 2-Azole derivatives with hypoglycemic and hypolipidemic activity |
| GB0221443D0 (en) | 2002-09-16 | 2002-10-23 | Glaxo Group Ltd | Pyridine derivates |
| UA82292C2 (uk) * | 2004-04-14 | 2008-03-25 | Пфайзер Продактс Инк. | Спосіб стереоселективного біоперетворення аліфатичних динітрилів в ціанокарбонові кислоти (варіанти) |
| WO2005113519A1 (en) | 2004-05-14 | 2005-12-01 | Irm Llc | Compounds and compositions as ppar modulators |
| ATE415385T1 (de) | 2004-10-01 | 2008-12-15 | Hoffmann La Roche | Hexafluorisopropanolsubstituierte etherderivate |
| DE602006017694D1 (de) | 2005-06-27 | 2010-12-02 | Bristol Myers Squibb Co | C-verknüpfte zyklische antagonisten des p2y1-rezeptors mit eignung bei der behandlung thrombotischer leiden |
| EP1931661B1 (en) | 2005-09-19 | 2008-11-19 | F.Hoffmann-La Roche Ag | Isoxazolo derivatives as gaba a alpha5 inverse agonists |
| WO2007042420A1 (en) | 2005-10-11 | 2007-04-19 | F. Hoffmann-La Roche Ag | Isoxazole derivatives |
| RU2426731C2 (ru) | 2005-12-23 | 2011-08-20 | Ф. Хоффманн-Ля Рош Аг | Производные арил-изоксазоло-4-ил-оксадиазола |
| WO2009071464A1 (en) | 2007-12-04 | 2009-06-11 | F. Hoffmann-La Roche Ag | Isoxazolo-pyrazine derivatives |
| US7943619B2 (en) | 2007-12-04 | 2011-05-17 | Hoffmann-La Roche Inc. | Isoxazolo-pyridazine derivatives |
| UA100132C2 (en) * | 2007-12-04 | 2012-11-26 | Ф. Хоффманн-Ля Рош Аг | Isoxazolo-pyridine derivatives |
| JP2012040448A (ja) * | 2008-11-14 | 2012-03-01 | Yasutaka Sakamoto | マイクロバブル発生装置 |
| US8222246B2 (en) | 2009-04-02 | 2012-07-17 | Hoffmann-La Roche Inc. | Substituted isoxazoles |
| MX2011011484A (es) | 2009-05-07 | 2011-11-18 | Hoffmann La Roche | Derivados de isoxazol-piridina como moduladores del acido gamma-aminobutirico. |
-
2012
- 2012-10-12 US US13/650,202 patent/US8604062B2/en active Active
- 2012-10-17 KR KR1020147013309A patent/KR20140084209A/ko not_active Ceased
- 2012-10-17 EP EP12772788.1A patent/EP2768827B1/en active Active
- 2012-10-17 DK DK12772788.1T patent/DK2768827T3/en active
- 2012-10-17 CA CA3112072A patent/CA3112072C/en active Active
- 2012-10-17 WO PCT/EP2012/070521 patent/WO2013057123A1/en not_active Ceased
- 2012-10-17 RU RU2014118966/04A patent/RU2014118966A/ru not_active Application Discontinuation
- 2012-10-17 HU HUE12772788A patent/HUE031276T2/hu unknown
- 2012-10-17 MY MYPI2014001152A patent/MY164880A/en unknown
- 2012-10-17 SG SG11201401626UA patent/SG11201401626UA/en unknown
- 2012-10-17 AR ARP120103859A patent/AR088358A1/es active IP Right Grant
- 2012-10-17 CA CA2850440A patent/CA2850440C/en active Active
- 2012-10-17 PL PL12772788T patent/PL2768827T3/pl unknown
- 2012-10-17 BR BR112014009266-4A patent/BR112014009266B1/pt active IP Right Grant
- 2012-10-17 SI SI201230864A patent/SI2768827T1/sl unknown
- 2012-10-17 MX MX2014004688A patent/MX2014004688A/es unknown
- 2012-10-17 AU AU2012321095A patent/AU2012321095B2/en active Active
- 2012-10-17 CN CN201280051438.1A patent/CN103889978B/zh active Active
- 2012-10-17 ES ES12772788.1T patent/ES2613802T3/es active Active
- 2012-10-17 JP JP2014536208A patent/JP5923174B2/ja active Active
- 2012-10-17 KR KR1020207001557A patent/KR102262697B1/ko active Active
-
2014
- 2014-03-20 IL IL231645A patent/IL231645A/en active IP Right Grant
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2014530831A5 (https=) | ||
| AU2004272338B2 (en) | Pyrrol derivatives with antibacterial activity | |
| CN104583197B (zh) | 新型双环吡啶衍生物 | |
| US8772291B2 (en) | Multicyclic compounds and methods of their use | |
| JP2013528591A5 (https=) | ||
| EP2073811A2 (en) | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases | |
| RU2014118966A (ru) | Способ получения изоксазолил-метокси-никотиновых кислот | |
| JP2013544840A5 (https=) | ||
| JP2018519323A5 (https=) | ||
| TW201215602A (en) | Novel nicotinamide derivative or salt thereof | |
| MX2012008280A (es) | Compuestos y metodos. | |
| TW200524872A (en) | Process for preparation of pyridine derivatives | |
| JP2008509955A5 (https=) | ||
| JP2003526601A5 (https=) | ||
| CN104350040B (zh) | 芳环化合物 | |
| NZ622214B2 (en) | Process for the preparation of isoxazolyl-methoxy-nicotinic acids | |
| HK1193610B (en) | Process for the preparation of isoxazolyl-methoxy-nicotinic acids |