JP2010526142A5 - - Google Patents
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- 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
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- 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
- 238000000034 method Methods 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 19
- 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 6
- MUUWQYQRBFVTIB-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1h-pyrrole Chemical compound CC1=CCCN1 MUUWQYQRBFVTIB-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 239000012458 free base Substances 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- XUKROCVZGZNGSI-CQSZACIVSA-N irdabisant 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 7
- 229910052697 platinum Inorganic materials 0.000 claims 3
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 claims 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims 2
- 230000003287 optical effect 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-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 42
- 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 atom Chemical group C* 0.000 description 12
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 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
- 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
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052802 copper Inorganic materials 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 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
- 230000008025 crystallization Effects 0.000 description 5
- 229960001270 d- tartaric acid Drugs 0.000 description 5
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 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
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-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
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229960003540 oxyquinoline Drugs 0.000 description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 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
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- KFHYZKCRXNRKRC-MRXNPFEDSA-N abt-239 Chemical compound C[C@@H]1CCCN1CCC1=CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2O1 KFHYZKCRXNRKRC-MRXNPFEDSA-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
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 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
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005842 heteroatom 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
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 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
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 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
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-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
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-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
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-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
- 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
- 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
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 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
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
- LUTSRLYCMSCGCS-BWOMAWGNSA-N [(3s,8r,9s,10r,13s)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC=C3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 LUTSRLYCMSCGCS-BWOMAWGNSA-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
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 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
- 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
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 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
- 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
- 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
- 229920006395 saturated elastomer Polymers 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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 |
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| JP2010526142A JP2010526142A (ja) | 2010-07-29 |
| JP2010526142A5 true JP2010526142A5 (enExample) | 2011-06-23 |
| JP5698887B2 JP5698887B2 (ja) | 2015-04-08 |
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| EP (1) | EP2152669A1 (enExample) |
| JP (1) | JP5698887B2 (enExample) |
| KR (1) | KR20100017565A (enExample) |
| CN (1) | CN101679237A (enExample) |
| AU (1) | AU2008248168B2 (enExample) |
| BR (1) | BRPI0810330A2 (enExample) |
| CA (1) | CA2686033A1 (enExample) |
| EA (1) | EA019031B1 (enExample) |
| IL (1) | IL201627A (enExample) |
| MX (1) | MX2009011787A (enExample) |
| NZ (1) | NZ580948A (enExample) |
| UA (1) | UA99913C2 (enExample) |
| WO (1) | WO2008137087A1 (enExample) |
| ZA (1) | ZA200907643B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ574873A (en) | 2006-07-25 | 2012-03-30 | Cephalon Inc | Pyridazinone derivatives as h3 inhibitors |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| ES2479440T3 (es) * | 2008-01-30 | 2014-07-24 | Cephalon, Inc. | Derivados de piridazina sustituidos que tienen actividad antagonista de histamina H3 |
| US10259794B2 (en) * | 2014-12-23 | 2019-04-16 | Cephalon, Inc. | Methods for preparing fused bicyclic 2, 4-diaminopyrimidine derivatives |
| KR20210057032A (ko) * | 2018-09-07 | 2021-05-20 | 사노피 | 메틸 6-(2,4-디클로로페닐)-5-[4-[(3s)-1-(3-플루오로프로필)피롤리딘-3-일]옥시페닐]-8,9-디히드로-7h-벤조[7]아눌렌-2-카르복실레이트의 염 및 이의 제조 방법 |
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 |
| US8110519B2 (en) | 2004-03-08 | 2012-02-07 | Japan Science & Technology Agency | Polymer-supported metal cluster composition |
| 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 |
| CN1960727B (zh) | 2004-06-02 | 2011-02-16 | 霍夫曼-拉罗奇有限公司 | 用作组胺-3受体的配体的萘衍生物 |
| US8158652B2 (en) | 2004-12-01 | 2012-04-17 | Msd K.K. | Substituted pyridone derivative |
| DE602005026169D1 (de) | 2004-12-17 | 2011-03-10 | Janssen Pharmaceutica Nv | Tetrahydroisochinolinverbindungen zur behandlung von zns-erkrankungen |
| CA2595157A1 (en) | 2005-01-21 | 2006-07-27 | Schering Corporation | Imidazole and benzimidazole derivatives useful as histamine h3 antagonists |
| 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 |
| WO2007048595A1 (en) | 2005-10-27 | 2007-05-03 | Ucb Pharma, S.A. | Compounds comprising a lactam or a lactam derivative moiety, processes for making them, and their uses |
| US7897634B2 (en) | 2006-02-09 | 2011-03-01 | 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 |
| NZ574873A (en) * | 2006-07-25 | 2012-03-30 | Cephalon Inc | Pyridazinone derivatives as h3 inhibitors |
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- 2008-05-02 AU AU2008248168A patent/AU2008248168B2/en not_active Ceased
- 2008-05-02 KR KR1020097025141A patent/KR20100017565A/ko not_active Ceased
- 2008-05-02 BR BRPI0810330-5A2A patent/BRPI0810330A2/pt not_active IP Right Cessation
- 2008-05-02 EP EP08754205A patent/EP2152669A1/en not_active Withdrawn
- 2008-05-02 MX MX2009011787A patent/MX2009011787A/es active IP Right Grant
- 2008-05-02 UA UAA200912476A patent/UA99913C2/ru unknown
- 2008-05-02 NZ NZ580948A patent/NZ580948A/en not_active IP Right Cessation
- 2008-05-02 WO PCT/US2008/005702 patent/WO2008137087A1/en not_active Ceased
- 2008-05-02 EA EA200971019A patent/EA019031B1/ru not_active IP Right Cessation
- 2008-05-02 CN CN200880021225A patent/CN101679237A/zh active Pending
- 2008-05-02 CA CA002686033A patent/CA2686033A1/en not_active Abandoned
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- 2009-10-19 IL IL201627A patent/IL201627A/en not_active IP Right Cessation
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