JP2010526142A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2010526142A5 JP2010526142A5 JP2010507416A JP2010507416A JP2010526142A5 JP 2010526142 A5 JP2010526142 A5 JP 2010526142A5 JP 2010507416 A JP2010507416 A JP 2010507416A JP 2010507416 A JP2010507416 A JP 2010507416A JP 2010526142 A5 JP2010526142 A5 JP 2010526142A5
- Authority
- JP
- Japan
- Prior art keywords
- methylpyrrolidine
- tartrate
- phenyl
- optionally
- alkyl
- 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
- AVAOHVDRAKDFRF-KLPPUMKISA-N (2R,3R)-2,3-dihydroxybutanedioic acid;(2R)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1.OC(=O)[C@H](O)[C@@H](O)C(O)=O AVAOHVDRAKDFRF-KLPPUMKISA-N 0.000 claims description 53
- 239000003054 catalyst Substances 0.000 claims description 24
- RGHPCLZJAFCTIK-RXMQYKEDSA-N (R)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1 RGHPCLZJAFCTIK-RXMQYKEDSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 16
- 238000005984 hydrogenation reaction Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- -1 2-methyl-pyrrolidin-1-yl Chemical group 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N (+)-tartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- MUUWQYQRBFVTIB-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1H-pyrrole Chemical compound CC1=CCCN1 MUUWQYQRBFVTIB-UHFFFAOYSA-N 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- XUKROCVZGZNGSI-CQSZACIVSA-N 3-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1H-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1 XUKROCVZGZNGSI-CQSZACIVSA-N 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 6
- 229910052697 platinum Inorganic materials 0.000 claims 3
- HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxalate, Glyoxylate Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims 1
- TXFPEBPIARQUIG-UHFFFAOYSA-N Piceol Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 claims 1
- 230000003287 optical Effects 0.000 claims 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical group [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 claims 1
- 229910003446 platinum oxide Inorganic materials 0.000 claims 1
- RGHPCLZJAFCTIK-YFKPBYRVSA-N (2S)-2-methylpyrrolidine Chemical compound C[C@H]1CCCN1 RGHPCLZJAFCTIK-YFKPBYRVSA-N 0.000 description 55
- FEWJPZIEWOKRBE-LWMBPPNESA-N (-)-tartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 47
- 125000000217 alkyl group Chemical group 0.000 description 41
- 150000001875 compounds Chemical class 0.000 description 25
- 239000000243 solution Substances 0.000 description 17
- 125000004432 carbon atoms Chemical group C* 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 9
- RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical compound CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000875 corresponding Effects 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
- 229910052802 copper Inorganic materials 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000002194 synthesizing Effects 0.000 description 6
- 229960001270 D- TARTARIC ACID Drugs 0.000 description 5
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000005712 crystallization Effects 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- OOGWMAIYWGZDRX-CYBMUJFWSA-N (2R)-1-[2-(6-bromonaphthalen-2-yl)ethyl]-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1CCC1=CC=C(C=C(Br)C=C2)C2=C1 OOGWMAIYWGZDRX-CYBMUJFWSA-N 0.000 description 3
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-Naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N 8-Hydroxyquinoline Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 3
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 3
- 125000004429 atoms Chemical group 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229960003540 oxyquinoline Drugs 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- AVAOHVDRAKDFRF-LREBCSMRSA-N (2R,3R)-2,3-dihydroxybutanedioic acid;2-methylpyrrolidine Chemical compound CC1CCCN1.OC(=O)[C@H](O)[C@@H](O)C(O)=O AVAOHVDRAKDFRF-LREBCSMRSA-N 0.000 description 2
- NISULOSDVFYWIH-NUFNRNBZSA-N (2R,3R)-2,3-dihydroxybutanedioic acid;4-[2-[2-[(2R)-2-methylpyrrolidin-1-yl]ethyl]-1-benzofuran-5-yl]benzonitrile Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C[C@@H]1CCCN1CCC1=CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2O1 NISULOSDVFYWIH-NUFNRNBZSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1H-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-Methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M Copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N Copper(I) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L Copper(II) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L Copper(II) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L Copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M Lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N Sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 231100000078 corrosive Toxicity 0.000 description 2
- 231100001010 corrosive Toxicity 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N ethoxyethane;trifluoroborane Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatoms Chemical group 0.000 description 2
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000001184 potassium carbonate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical group CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 2
- 239000003638 reducing agent Substances 0.000 description 2
- 239000001187 sodium carbonate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001131 transforming Effects 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JNEIFWYJFOEKIM-NUBCRITNSA-N (2R)-2-methylpyrrolidine;hydrochloride Chemical compound Cl.C[C@@H]1CCCN1 JNEIFWYJFOEKIM-NUBCRITNSA-N 0.000 description 1
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-Tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- FHWHVTPFLXCNAN-UHFFFAOYSA-N 1-[3-[[1-(2-methylpyrrolidin-1-yl)-2,3-dihydro-1H-inden-5-yl]oxy]propyl]azepane Chemical compound CC1CCCN1C1C2=CC=C(OCCCN3CCCCCC3)C=C2CC1 FHWHVTPFLXCNAN-UHFFFAOYSA-N 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N 2,2'-bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-Methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- XUKROCVZGZNGSI-AWEZNQCLSA-N 3-[4-[3-[(2S)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1H-pyridazin-6-one Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1 XUKROCVZGZNGSI-AWEZNQCLSA-N 0.000 description 1
- FRPCIFNVZOTRLB-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-methyl-7-[3-(2-methylpyrrolidin-1-yl)propoxy]-3,4-dihydro-1H-isoquinoline Chemical compound C1=CC(OC)=CC=C1C1C2=CC=C(OCCCN3C(CCC3)C)C=C2CN(C)C1 FRPCIFNVZOTRLB-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-Methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- LUOZEWPJSYBORW-UHFFFAOYSA-N 7-methylquinolin-8-ol Chemical compound C1=CC=NC2=C(O)C(C)=CC=C21 LUOZEWPJSYBORW-UHFFFAOYSA-N 0.000 description 1
- OKPSVYHYNXVYED-UHFFFAOYSA-N 7-propylquinolin-8-ol Chemical compound C1=CC=NC2=C(O)C(CCC)=CC=C21 OKPSVYHYNXVYED-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N Benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L Caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate dianion Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M Copper(I) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M Copper(I) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N DMA Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N Ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- WCJAYABJWDIZAJ-UHFFFAOYSA-N Lithium triethylborohydride Chemical compound [Li+].CC[BH-](CC)CC WCJAYABJWDIZAJ-UHFFFAOYSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N OBO Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 230000001808 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N n-methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- VLYFRFHWUBBLRR-UHFFFAOYSA-L potassium;sodium;carbonate Chemical compound [Na+].[K+].[O-]C([O-])=O VLYFRFHWUBBLRR-UHFFFAOYSA-L 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- YOQDYZUWIQVZSF-UHFFFAOYSA-N sodium borohydride Substances [BH4-].[Na+] YOQDYZUWIQVZSF-UHFFFAOYSA-N 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
- ODGROJYWQXFQOZ-UHFFFAOYSA-N sodium;boron(1-) Chemical compound [B-].[Na+] ODGROJYWQXFQOZ-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- BFFLLBPMZCIGRM-QMMMGPOBSA-N tert-butyl (2S)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CO BFFLLBPMZCIGRM-QMMMGPOBSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003953 γ-lactams Chemical class 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92735607P | 2007-05-03 | 2007-05-03 | |
| US60/927,356 | 2007-05-03 | ||
| PCT/US2008/005702 WO2008137087A1 (en) | 2007-05-03 | 2008-05-02 | Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010526142A JP2010526142A (ja) | 2010-07-29 |
| JP2010526142A5 true JP2010526142A5 (sk) | 2011-06-23 |
| JP5698887B2 JP5698887B2 (ja) | 2015-04-08 |
Family
ID=39688886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010507416A Expired - Fee Related JP5698887B2 (ja) | 2007-05-03 | 2008-05-02 | （ｒ）−２−メチルピロリジンおよび（ｓ）−２−メチルピロリジンならびにその酒石酸塩を調製するための方法 |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP2152669A1 (sk) |
| JP (1) | JP5698887B2 (sk) |
| KR (1) | KR20100017565A (sk) |
| CN (1) | CN101679237A (sk) |
| AU (1) | AU2008248168B2 (sk) |
| BR (1) | BRPI0810330A2 (sk) |
| CA (1) | CA2686033A1 (sk) |
| EA (1) | EA019031B1 (sk) |
| IL (1) | IL201627A (sk) |
| MX (1) | MX2009011787A (sk) |
| NZ (1) | NZ580948A (sk) |
| UA (1) | UA99913C2 (sk) |
| WO (1) | WO2008137087A1 (sk) |
| ZA (1) | ZA200907643B (sk) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2069312T1 (sl) | 2006-07-25 | 2013-03-29 | Cephalon, Inc. | Derivati piridizinona |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| EP2752406A1 (en) * | 2008-01-30 | 2014-07-09 | Cephalon, Inc. | Substituted pyridazine derivatives which have histamine H3 antagonist activity |
| US10259794B2 (en) * | 2014-12-23 | 2019-04-16 | Cephalon, Inc. | Methods for preparing fused bicyclic 2, 4-diaminopyrimidine derivatives |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3329974A1 (de) | 1983-08-19 | 1985-02-28 | Bayer Ag, 5090 Leverkusen | Herstellung von hydrierten nitrilkautschuken |
| DE3433392A1 (de) | 1984-09-12 | 1986-03-20 | Bayer Ag, 5090 Leverkusen | Hydrierung nitrilgruppenhaltiger ungesaettigter polymerer |
| FR2714849B1 (fr) | 1994-01-13 | 1996-04-05 | Inst Francais Du Petrole | Procédé de préparation d'un catalyseur d'hydrogénation soluble en phase liquide organique. |
| DE4403479A1 (de) | 1994-02-04 | 1995-08-10 | Basf Ag | Verfahren zur Herstellung von Hydroxylammoniumsalzen |
| WO2004024707A2 (en) * | 2002-09-16 | 2004-03-25 | Abbott Laboratories | Process for preparing amine type substituted benzofurans |
| US7153889B2 (en) | 2002-11-12 | 2006-12-26 | Abbott Laboratories | Bicyclic-substituted amines as histamine-3 receptor ligands |
| CN100543050C (zh) | 2004-03-08 | 2009-09-23 | 独立行政法人科学技术振兴机构 | 高分子担载金属簇组合物 |
| US7145005B2 (en) | 2004-05-12 | 2006-12-05 | Abbott Laboratories | 2-(6-{2-[(2R)-2-Methyl-1-pyrrolidin-1-yl]-ethyl}-2-naphthalen-2-yl)-2H-pyridazin-3-one salts and their preparation |
| JP4594386B2 (ja) | 2004-06-02 | 2010-12-08 | エフ．ホフマン−ラ ロシュ アーゲー | ヒスタミン３受容体のリガンドとして有用なナフタレン誘導体 |
| JPWO2006059778A1 (ja) | 2004-12-01 | 2008-06-05 | 萬有製薬株式会社 | 置換ピリドン誘導体 |
| WO2006066197A1 (en) | 2004-12-17 | 2006-06-22 | Janssen Pharmaceutica, N.V. | Tetrahydroisoquinoline compounds for treatment of cns disorders |
| CN101107231A (zh) | 2005-01-21 | 2008-01-16 | 先灵公司 | 用作组胺h3拮抗剂的咪唑和苯并咪唑衍生物 |
| EP1866293A1 (en) | 2005-03-31 | 2007-12-19 | UCB Pharma, S.A. | Compounds comprising an oxazole or thiazole moiety, processes for making them, and their uses |
| GB0514812D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| JP2009513590A (ja) | 2005-10-27 | 2009-04-02 | ユセベ ファルマ ソシエテ アノニム | ラクタム又はラクタム誘導体部分を含む化合物、これらの製造方法、及びこれらの使用 |
| WO2007094962A2 (en) | 2006-02-09 | 2007-08-23 | Athersys, Inc. | Pyrazoles for the treatment of obesity and other cns disorders |
| WO2007099423A1 (en) | 2006-03-02 | 2007-09-07 | Pfizer Products Inc. | 1-pyrrolidine indane derivatives as histamine-3 receptor antagonists |
| US20090163482A1 (en) | 2006-03-13 | 2009-06-25 | Mchardy Stanton Furst | Tetralines antagonists of the h-3 receptor |
| WO2008005338A1 (en) | 2006-06-29 | 2008-01-10 | Arena Pharmaceuticals, Inc. | Modulators of the histamine h3-receptor useful for the treatment of disorders related thereto |
| SI2069312T1 (sl) * | 2006-07-25 | 2013-03-29 | Cephalon, Inc. | Derivati piridizinona |
-
2008
- 2008-05-02 WO PCT/US2008/005702 patent/WO2008137087A1/en active Application Filing
- 2008-05-02 MX MX2009011787A patent/MX2009011787A/es active IP Right Grant
- 2008-05-02 JP JP2010507416A patent/JP5698887B2/ja not_active Expired - Fee Related
- 2008-05-02 KR KR1020097025141A patent/KR20100017565A/ko not_active Application Discontinuation
- 2008-05-02 EP EP08754205A patent/EP2152669A1/en not_active Withdrawn
- 2008-05-02 CN CN200880021225A patent/CN101679237A/zh active Pending
- 2008-05-02 CA CA002686033A patent/CA2686033A1/en not_active Abandoned
- 2008-05-02 NZ NZ580948A patent/NZ580948A/en not_active IP Right Cessation
- 2008-05-02 EA EA200971019A patent/EA019031B1/ru not_active IP Right Cessation
- 2008-05-02 AU AU2008248168A patent/AU2008248168B2/en not_active Ceased
- 2008-05-02 UA UAA200912476A patent/UA99913C2/ru unknown
- 2008-05-02 BR BRPI0810330-5A2A patent/BRPI0810330A2/pt not_active IP Right Cessation
-
2009
- 2009-10-19 IL IL201627A patent/IL201627A/en not_active IP Right Cessation
- 2009-10-30 ZA ZA2009/07643A patent/ZA200907643B/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7413363B2 (ja) | メチル６－（２，４－ジクロロフェニル）－５－［４－［（３ｓ）－１－（３－フルオロプロピル）ピロリジン－３－イル］オキシフェニル］－８，９－ジヒドロ－７ｈ－ベンゾ［７］アヌレン－２－カルボキシレートの調製方法 | |
| JP2786480B2 (ja) | １―インドリルアルキル―４―（置換ピリジニル）ピペラジン | |
| JP3085708B2 (ja) | ピペラジン誘導体 | |
| TWI823911B (zh) | 製備方法 | |
| ES2561834T3 (es) | Naftiridonas y quinolonas 7-amino alquilidenil-heterocíclicas | |
| RU2480461C2 (ru) | Способ получения иматиниба и его промежуточных соединений | |
| JP2011042671A (ja) | ピリジルテトラヒドロピリジン類及びピリジルピペリジン類とそれらの製造方法 | |
| SK285433B6 (sk) | Spôsob prípravy bifenylových derivátov vhodných na prípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínov | |
| JPH10503501A (ja) | 抗喘息、抗アレルギー、抗炎症及び免疫修飾作用を有するインドール、インダゾール、ピリドピロール及びピリドピラゾール誘導体 | |
| HUT65837A (en) | Process for producing phenoxy- and phenoxyalkyl-piperidines and pharmaceutical preparations containing them | |
| JP3269574B2 (ja) | メタノアントラセン化合物、これを含有する神経精神障害を治療するための調剤学的組成物、およびこの化合物を製造するための方法および中間体 | |
| JP2010526142A5 (sk) | ||
| KR20100103646A (ko) | ６치환된１（２ｈ）이소퀴놀리논의 제조 방법 | |
| JP2002535365A (ja) | 抗うつ性複素環化合物 | |
| ZA200308634B (en) | 4-(phenyl-piperidin-4-ylidene-methyl)-benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders. | |
| JP5698887B2 (ja) | （ｒ）−２−メチルピロリジンおよび（ｓ）−２−メチルピロリジンならびにその酒石酸塩を調製するための方法 | |
| KR20150046456A (ko) | 신규한 항진균성 옥소다이하이드로피리딘카보하이드라자이드 유도체 | |
| EP2509973A1 (en) | Process for the preparation of imatinib and salts thereof | |
| JP7252978B2 (ja) | ２－（１－（ｔｅｒｔ－ブトキシカルボニル）ピペリジン－４－イル）安息香酸を調製するためのプロセス | |
| SU680648A3 (ru) | Способ получени производных пиперидина или их кислотноаддитивных солей | |
| WO1984001945A1 (en) | Phenoxyaminopropanol derivatives | |
| JPS5838277A (ja) | スピロチアゾリジニルピペラジン誘導体 | |
| JPH01125366A (ja) | α−（アルキルフェニル）−４−（ヒドロキシジフェニルメチル）−１−ピペリジンブタノールの製造方法 | |
| SU587861A3 (ru) | Способ получени производных -диоксан-5-метиламина | |
| JP2840855B2 (ja) | ジヒドロピリジン誘導体の製造方法 |