JP2010513531A5 - - Google Patents
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- JP2010513531A5 JP2010513531A5 JP2009542959A JP2009542959A JP2010513531A5 JP 2010513531 A5 JP2010513531 A5 JP 2010513531A5 JP 2009542959 A JP2009542959 A JP 2009542959A JP 2009542959 A JP2009542959 A JP 2009542959A JP 2010513531 A5 JP2010513531 A5 JP 2010513531A5
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- compounds
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- 238000000034 method Methods 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 238000006243 chemical reaction Methods 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000010948 rhodium Substances 0.000 claims description 9
- 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 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000001099 ammonium carbonate Substances 0.000 claims description 4
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 239000011833 salt mixture Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- -1 1-amino, 3-substituted phenylcyclopentanecarboxylic esters Chemical class 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- OVMPLGZIMNITFL-DGCLKSJQSA-N (1r,3r)-1-amino-3-(4-methoxyphenyl)cyclopentane-1-carbonitrile Chemical compound C1=CC(OC)=CC=C1[C@H]1C[C@@](N)(C#N)CC1 OVMPLGZIMNITFL-DGCLKSJQSA-N 0.000 description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- GFOKSKMVRLJJNR-IINYFYTJSA-N (5r,8s)-8-(4-bromophenyl)-3-methyl-1,3-diazaspiro[4.4]nonane-2,4-dione Chemical compound O=C1N(C)C(=O)N[C@]11C[C@@H](C=2C=CC(Br)=CC=2)CC1 GFOKSKMVRLJJNR-IINYFYTJSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- VATJIJWNRANFNO-ZYHUDNBSSA-N (1r,3r)-1-amino-3-(4-bromophenyl)cyclopentane-1-carbonitrile Chemical compound C1[C@@](N)(C#N)CC[C@H]1C1=CC=C(Br)C=C1 VATJIJWNRANFNO-ZYHUDNBSSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 5
- 229940091173 hydantoin Drugs 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 0 CC(CC1)(C=C1C(OC)=O)c1ccc(*=C)cc1 Chemical compound CC(CC1)(C=C1C(OC)=O)c1ccc(*=C)cc1 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000000105 evaporative light scattering detection Methods 0.000 description 4
- 150000001469 hydantoins Chemical class 0.000 description 4
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- HXBKFSNTNCFTHX-JOYOIKCWSA-N (1r,3s)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylic acid Chemical compound C1[C@@](N)(C(O)=O)CC[C@@H]1C1=CC=C(Br)C=C1 HXBKFSNTNCFTHX-JOYOIKCWSA-N 0.000 description 3
- AJKPXKHWCHZLSF-VIFPVBQESA-N (3s)-3-(4-bromophenyl)cyclopentan-1-one Chemical compound C1=CC(Br)=CC=C1[C@@H]1CC(=O)CC1 AJKPXKHWCHZLSF-VIFPVBQESA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- DXRSYLNLGBXYNJ-GWCFXTLKSA-N methyl (1s,3s)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate Chemical compound C1[C@@](C(=O)OC)(N)CC[C@@H]1C1=CC=C(Br)C=C1 DXRSYLNLGBXYNJ-GWCFXTLKSA-N 0.000 description 3
- IIHIJFJSXPDTNO-UHFFFAOYSA-N methyl cyclopentanecarboxylate Chemical compound COC(=O)C1CCCC1 IIHIJFJSXPDTNO-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- KRZRJGAVKAKWTO-HTMVYDOJSA-N (1R,3R)-1-amino-3-(4-methoxyphenyl)cyclopentane-1-carboxylic acid hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1[C@H]1C[C@@](N)(C(O)=O)CC1 KRZRJGAVKAKWTO-HTMVYDOJSA-N 0.000 description 2
- YYWBOYFAACOYTR-ZWNOBZJWSA-N (1r,3r)-1-amino-3-(4-methoxyphenyl)cyclopentane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1[C@H]1C[C@@](N)(C(O)=O)CC1 YYWBOYFAACOYTR-ZWNOBZJWSA-N 0.000 description 2
- ZZMYWYZPNZRYPX-SANMLTNESA-N (2r)-2-amino-2-[5-[4-[2-(4-phenylphenyl)ethoxy]-3-(trifluoromethyl)phenyl]-1h-imidazol-2-yl]propan-1-ol Chemical compound N1C([C@@](N)(CO)C)=NC=C1C(C=C1C(F)(F)F)=CC=C1OCCC1=CC=C(C=2C=CC=CC=2)C=C1 ZZMYWYZPNZRYPX-SANMLTNESA-N 0.000 description 2
- BXVGGHJBRCDSGU-SNVBAGLBSA-N (3r)-3-(4-methoxyphenyl)cyclopentan-1-one Chemical compound C1=CC(OC)=CC=C1[C@H]1CC(=O)CC1 BXVGGHJBRCDSGU-SNVBAGLBSA-N 0.000 description 2
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 2
- LNBAOWJYCPKZOS-NCWAPJAISA-N (5s)-8-(4-bromophenyl)-1,3-diazaspiro[4.4]nonane-2,4-dione Chemical compound C1=CC(Br)=CC=C1C1C[C@]2(C(NC(=O)N2)=O)CC1 LNBAOWJYCPKZOS-NCWAPJAISA-N 0.000 description 2
- GFOKSKMVRLJJNR-HZMBPMFUSA-N (5s,8s)-8-(4-bromophenyl)-3-methyl-1,3-diazaspiro[4.4]nonane-2,4-dione Chemical compound O=C1N(C)C(=O)N[C@@]11C[C@@H](C=2C=CC(Br)=CC=2)CC1 GFOKSKMVRLJJNR-HZMBPMFUSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- IOAMXHPKIUMBMD-NHYWBVRUSA-N C=C[C@](CC1)(C[C@H]1c(cc1)ccc1Br)C(NC(N)=O)=O Chemical compound C=C[C@](CC1)(C[C@H]1c(cc1)ccc1Br)C(NC(N)=O)=O IOAMXHPKIUMBMD-NHYWBVRUSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentane carboxylic acid Natural products OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- AFQSOHSPTULSFS-FGSKAQBVSA-N ethene;(z)-4-hydroxypent-3-en-2-one;rhodium Chemical compound [Rh].C=C.C=C.C\C(O)=C\C(C)=O AFQSOHSPTULSFS-FGSKAQBVSA-N 0.000 description 2
- AILKHAQXUAOOFU-UHFFFAOYSA-N hexanenitrile Chemical compound CCCCCC#N AILKHAQXUAOOFU-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- DXLOKEVVKYIAPJ-SMDQHNSPSA-N methyl (1r,3s)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C1[C@](C(=O)OC)(N)CC[C@@H]1C1=CC=C(Br)C=C1 DXLOKEVVKYIAPJ-SMDQHNSPSA-N 0.000 description 2
- DXRSYLNLGBXYNJ-MFKMUULPSA-N methyl (1s,3r)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate Chemical compound C1[C@@](C(=O)OC)(N)CC[C@H]1C1=CC=C(Br)C=C1 DXRSYLNLGBXYNJ-MFKMUULPSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- VOZQBNOLRVKBGT-WYUVZMMLSA-N (1R,3R)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylic acid hydrochloride Chemical compound Cl.C1[C@@](N)(C(O)=O)CC[C@H]1C1=CC=C(Br)C=C1 VOZQBNOLRVKBGT-WYUVZMMLSA-N 0.000 description 1
- RZPPTYZARIWQCK-KOLCDFICSA-N (1S,3R)-3-(4-bromophenyl)cyclopentan-1-amine Chemical compound N[C@H]1CC[C@H](C1)c1ccc(Br)cc1 RZPPTYZARIWQCK-KOLCDFICSA-N 0.000 description 1
- PWEFCMHUAJTXTC-MNOVXSKESA-N (1S,3R)-3-(4-methoxyphenyl)cyclopentan-1-amine Chemical compound COc1ccc(cc1)[C@@H]1CC[C@H](N)C1 PWEFCMHUAJTXTC-MNOVXSKESA-N 0.000 description 1
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 description 1
- OVMPLGZIMNITFL-YPMHNXCESA-N (1s,3r)-1-amino-3-(4-methoxyphenyl)cyclopentane-1-carbonitrile Chemical compound C1=CC(OC)=CC=C1[C@H]1C[C@](N)(C#N)CC1 OVMPLGZIMNITFL-YPMHNXCESA-N 0.000 description 1
- AJKPXKHWCHZLSF-SECBINFHSA-N (3r)-3-(4-bromophenyl)cyclopentan-1-one Chemical compound C1=CC(Br)=CC=C1[C@H]1CC(=O)CC1 AJKPXKHWCHZLSF-SECBINFHSA-N 0.000 description 1
- OOZQSVXPBCINJF-UHFFFAOYSA-N 1-bromo-4-octylbenzene Chemical compound CCCCCCCCC1=CC=C(Br)C=C1 OOZQSVXPBCINJF-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- YYWBOYFAACOYTR-GWCFXTLKSA-N C1=CC(OC)=CC=C1[C@@H]1C[C@](N)(C(O)=O)CC1 Chemical class C1=CC(OC)=CC=C1[C@@H]1C[C@](N)(C(O)=O)CC1 YYWBOYFAACOYTR-GWCFXTLKSA-N 0.000 description 1
- PKGWZXNPDCYMSH-SECBINFHSA-N C[C@H](CCNC(NC=O)=O)c(cc1)ccc1Br Chemical compound C[C@H](CCNC(NC=O)=O)c(cc1)ccc1Br PKGWZXNPDCYMSH-SECBINFHSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- DRUFIZLVYAZXGE-JDRUZZMFSA-N O=C([C@](CC1)(C[C@H]1C1C=CC(Br)=CC1)N1)NC1=O Chemical compound O=C([C@](CC1)(C[C@H]1C1C=CC(Br)=CC1)N1)NC1=O DRUFIZLVYAZXGE-JDRUZZMFSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- RJYZHZIMHNKPKM-UHFFFAOYSA-N [Rh].C=C Chemical compound [Rh].C=C RJYZHZIMHNKPKM-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- JBDSSBMEKXHSJF-UHFFFAOYSA-M cyclopentanecarboxylate Chemical compound [O-]C(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-M 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- FUJCRWPEOMXPAD-UHFFFAOYSA-N lithium oxide Chemical compound [Li+].[Li+].[O-2] FUJCRWPEOMXPAD-UHFFFAOYSA-N 0.000 description 1
- 229910001947 lithium oxide Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
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- DXRSYLNLGBXYNJ-GXFFZTMASA-N methyl (1r,3s)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate Chemical compound C1[C@](C(=O)OC)(N)CC[C@@H]1C1=CC=C(Br)C=C1 DXRSYLNLGBXYNJ-GXFFZTMASA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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| US87625106P | 2006-12-21 | 2006-12-21 | |
| PCT/US2007/026257 WO2008079380A1 (en) | 2006-12-21 | 2007-12-21 | Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane carboxylates |
Publications (2)
| Publication Number | Publication Date |
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| JP2010513531A JP2010513531A (ja) | 2010-04-30 |
| JP2010513531A5 true JP2010513531A5 (enExample) | 2011-03-24 |
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| Country | Link |
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| EP (1) | EP2102145A4 (enExample) |
| JP (1) | JP2010513531A (enExample) |
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| CA (1) | CA2673076A1 (enExample) |
| MX (1) | MX2009006748A (enExample) |
| RU (1) | RU2009128063A (enExample) |
| WO (1) | WO2008079380A1 (enExample) |
| ZA (1) | ZA200903874B (enExample) |
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| JP6057912B2 (ja) * | 2010-12-22 | 2017-01-11 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | シス−１−アンモニウム−４−アルコキシシクロヘキサンカルボニトリル塩類を調製する方法 |
| CN107759483B (zh) * | 2016-08-16 | 2022-03-11 | 浙江瑞博制药有限公司 | 一种甲氨基取代的环戊烷甲酸烷基酯的制备方法 |
| CN115847629B (zh) * | 2022-11-30 | 2023-09-29 | 江苏富乐徳石英科技有限公司 | 一种高效节能环保的石英环制备工艺 |
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|---|---|---|---|---|
| US4841079A (en) * | 1987-08-07 | 1989-06-20 | Pfizer, Inc. | Process for the production of asymmetric hydantoins |
| AU2807192A (en) * | 1991-10-02 | 1993-05-03 | Smithkline Beecham Corporation | Cyclopentane and cyclopentene derivatives with antiallergic antiinflammatory and tumor necrosis factor inhibiting activity |
| US5314896A (en) | 1991-11-20 | 1994-05-24 | Warner-Lambert Company | 1,3-substituted cycloalkenes and cycloalkanes as central nervous system agents |
| US20020052370A1 (en) * | 2000-07-06 | 2002-05-02 | Barber Christopher Gordon | Cyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase |
| EP1188826B1 (en) * | 2000-09-13 | 2011-06-08 | Ajinomoto Co., Inc. | 5-substituted hydantoin racemase, DNA coding for the same, and process for producing optically active amino acids |
| EP1541692A1 (en) * | 2002-09-06 | 2005-06-15 | Kaneka Corporation | PROCESS FOR PRODUCING L-a-METHYLCYSTEINE DERIVATIVE |
| AR043050A1 (es) * | 2002-09-26 | 2005-07-13 | Rib X Pharmaceuticals Inc | Compuestos heterociclicos bifuncionales y metodos para preparar y usar los mismos |
| US7256198B2 (en) * | 2004-02-18 | 2007-08-14 | Wyeth | Pyrimidoindolones and methods for using same |
| AU2005315430B2 (en) * | 2004-12-14 | 2010-05-27 | Astrazeneca Ab | Oxadiazole derivatives as DGAT inhibitors |
| JP2008530135A (ja) | 2005-02-14 | 2008-08-07 | ユニバーシティ オブ バージニア パテント ファンデーション | アミノ基およびフェニル基で置換されたシクロアルカンならびに５員の複素環を含むスフィンゴシン＝１−リン酸アゴニスト |
| US7521557B2 (en) * | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
| EP1986623A2 (en) * | 2006-01-27 | 2008-11-05 | University Of Virginia Patent Foundation | Method for treatment of neuropathic pain |
| JP2009527501A (ja) * | 2006-02-21 | 2009-07-30 | ユニバーシティ オブ バージニア パテント ファンデーション | Ｓ１ｐ受容体アゴニストとしてのフェニル−シクロアルキル誘導体およびフェニル−複素環誘導体 |
| AU2007338700A1 (en) * | 2006-12-21 | 2008-07-03 | Abbott Laboratories | Sphingosine-1 -phosphate receptor agonist and antagonist compounds |
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- 2007-12-21 MX MX2009006748A patent/MX2009006748A/es active IP Right Grant
- 2007-12-21 RU RU2009128063/04A patent/RU2009128063A/ru not_active Application Discontinuation
- 2007-12-21 US US12/004,582 patent/US7956195B2/en not_active Expired - Fee Related
- 2007-12-21 EP EP07863231.2A patent/EP2102145A4/en not_active Withdrawn
- 2007-12-21 JP JP2009542959A patent/JP2010513531A/ja not_active Withdrawn
- 2007-12-21 CN CNA2007800467996A patent/CN101563316A/zh active Pending
- 2007-12-21 WO PCT/US2007/026257 patent/WO2008079380A1/en not_active Ceased
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2009
- 2009-06-03 ZA ZA200903874A patent/ZA200903874B/xx unknown
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