UA79774C2 - Process for preparation of chiral 1,4-disubstituted piperazines, intermediate (variants) - Google Patents
Process for preparation of chiral 1,4-disubstituted piperazines, intermediate (variants) Download PDFInfo
- Publication number
- UA79774C2 UA79774C2 UA20041008215A UA20041008215A UA79774C2 UA 79774 C2 UA79774 C2 UA 79774C2 UA 20041008215 A UA20041008215 A UA 20041008215A UA 20041008215 A UA20041008215 A UA 20041008215A UA 79774 C2 UA79774 C2 UA 79774C2
- Authority
- UA
- Ukraine
- Prior art keywords
- compound
- formula
- benzodioxin
- dihydro
- group
- Prior art date
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- -1 1,4-disubstituted piperazines Chemical class 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000008569 process Effects 0.000 title claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 230000000707 stereoselective effect Effects 0.000 claims abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 229910052700 potassium Inorganic materials 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 230000003993 interaction Effects 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 6
- 125000004970 halomethyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 150000004982 aromatic amines Chemical class 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- 150000002825 nitriles Chemical group 0.000 claims description 2
- 125000004385 trihaloalkyl group Chemical group 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 2
- HYSZWUPCSXTPSX-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)ethanol Chemical compound CCN1CCN(CCO)CC1 HYSZWUPCSXTPSX-UHFFFAOYSA-N 0.000 claims 1
- MYLBTCQBKAKUTJ-UHFFFAOYSA-N 7-methyl-6,8-bis(methylsulfanyl)pyrrolo[1,2-a]pyrazine Chemical compound C1=CN=CC2=C(SC)C(C)=C(SC)N21 MYLBTCQBKAKUTJ-UHFFFAOYSA-N 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 abstract 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 abstract 1
- 239000011230 binding agent Substances 0.000 abstract 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000543 intermediate Chemical class 0.000 description 9
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 150000004885 piperazines Chemical class 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- DMLRSJNZORFCBD-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-5-amine Chemical compound O1CCOC2=C1C=CC=C2N DMLRSJNZORFCBD-UHFFFAOYSA-N 0.000 description 7
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical class ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 7
- 239000012266 salt solution Substances 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 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 2
- 235000003351 Brassica cretica Nutrition 0.000 description 2
- 235000003343 Brassica rupestris Nutrition 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000009835 boiling Methods 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
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 235000010460 mustard Nutrition 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical class CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 2
- 150000008648 triflates Chemical class 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YGEIEDQEXUKJJA-UHFFFAOYSA-N 1,4-benzodioxin-3-amine Chemical compound C1=CC=C2OC(N)=COC2=C1 YGEIEDQEXUKJJA-UHFFFAOYSA-N 0.000 description 1
- CEZBCWUICWDAJI-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-3-amine Chemical compound C1=CC=C2OC(N)COC2=C1 CEZBCWUICWDAJI-UHFFFAOYSA-N 0.000 description 1
- YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
- OULBFTVYYKRYRX-UHFFFAOYSA-N 5-methyl-3-pyridin-2-yloxathiazolidine 2,2-dioxide Chemical compound O=S1(=O)OC(C)CN1C1=CC=CC=N1 OULBFTVYYKRYRX-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 241001377010 Pila Species 0.000 description 1
- DHYGRVBWQJXHIF-UHFFFAOYSA-N S(=O)(=O)(C(F)(F)F)O.C(C(O)C)(=O)O Chemical class S(=O)(=O)(C(F)(F)F)O.C(C(O)C)(=O)O DHYGRVBWQJXHIF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- QJAIURPMYMHDCD-UHFFFAOYSA-N tert-butyl 2-aminopyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CN=C1N QJAIURPMYMHDCD-UHFFFAOYSA-N 0.000 description 1
- ORUGTGTZBRUQIT-UHFFFAOYSA-N tert-butyl n-pyridin-2-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=N1 ORUGTGTZBRUQIT-UHFFFAOYSA-N 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/12—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C309/06—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing halogen atoms, or nitro or nitroso groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36345802P | 2002-03-12 | 2002-03-12 | |
| PCT/US2003/007176 WO2003078420A2 (en) | 2002-03-12 | 2003-03-10 | Process for making chiral 1,4-disubstituted piperazines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA79774C2 true UA79774C2 (en) | 2007-07-25 |
Family
ID=28041772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20041008215A UA79774C2 (en) | 2002-03-12 | 2003-10-03 | Process for preparation of chiral 1,4-disubstituted piperazines, intermediate (variants) |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US7019137B2 (xx) |
| EP (1) | EP1483256A2 (xx) |
| JP (1) | JP2005527530A (xx) |
| KR (1) | KR20040091119A (xx) |
| CN (2) | CN101492383A (xx) |
| AR (1) | AR038931A1 (xx) |
| AU (1) | AU2003220110B2 (xx) |
| BR (1) | BR0308347A (xx) |
| CA (1) | CA2477906A1 (xx) |
| CR (1) | CR7428A (xx) |
| EC (1) | ECSP045292A (xx) |
| IL (1) | IL163828A0 (xx) |
| MX (1) | MXPA04008730A (xx) |
| NO (1) | NO20043988L (xx) |
| NZ (1) | NZ535169A (xx) |
| RU (2) | RU2315044C2 (xx) |
| TW (1) | TW200304825A (xx) |
| UA (1) | UA79774C2 (xx) |
| WO (1) | WO2003078420A2 (xx) |
| ZA (1) | ZA200408205B (xx) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003007956A1 (en) | 2001-07-20 | 2003-01-30 | Psychogenics, Inc. | Treatment for attention-deficit hyperactivity disorder |
| US7361773B2 (en) * | 2002-03-12 | 2008-04-22 | Wyeth | Preparation of N1-(2'-pyridyl)-1,2-propanediamine sulfamic acid and its use in the synthesis of biologically active piperazines |
| CN101492383A (zh) * | 2002-03-12 | 2009-07-29 | 惠氏公司 | 制备手性1,4-二取代哌嗪的方法 |
| PA8626301A1 (es) * | 2004-03-19 | 2006-12-07 | Wyeth Wyeth | Proceso para preparar derivados de n-aril-piperazina |
| US20050215561A1 (en) * | 2004-03-19 | 2005-09-29 | Krishnendu Ghosh | Pharmaceutical dosage forms and compositions |
| US20070099931A1 (en) * | 2004-03-19 | 2007-05-03 | Wyeth | Pharmaceutical dosage forms and compositions |
| WO2008117269A2 (en) | 2007-03-28 | 2008-10-02 | Atir Holding S.A. | Heterotri cyciii c compounds as serotonergic and/or dopaminergic agents and uses thereof |
| CN108627380B (zh) * | 2017-03-15 | 2020-10-20 | 中国人民解放军军事医学科学院毒物药物研究所 | 去除或减少有毒物质的方法以及检测有毒物质的方法 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE960203C (de) * | 1953-12-25 | 1957-03-21 | Yoshitomi Pharmaceutical | Verfahren zur Herstellung von N-substituierten Aminocarbonsaeureestern |
| AU577802B2 (en) * | 1983-10-17 | 1988-10-06 | Duphar International Research B.V. | Blood-pressure lowering piperazine derivatives |
| DE3586794T2 (de) | 1984-12-21 | 1993-05-27 | Duphar Int Res | Arzneimittel mit psychotroper wirkung. |
| JPH01125357A (ja) | 1987-11-06 | 1989-05-17 | Dainippon Pharmaceut Co Ltd | トリペプチドの誘導体 |
| IL101722A (en) | 1991-05-02 | 1996-05-14 | Wyeth John & Brother Ltd | History of piperazine, their preparation and pharmaceutical preparations containing them |
| AU3904493A (en) * | 1992-04-13 | 1993-11-18 | Fujisawa Pharmaceutical Co., Ltd. | Substituted 3-pyrrolidinylthio-carbapenems as antimicrobial agents |
| GB9208740D0 (en) * | 1992-04-23 | 1992-06-10 | Glaxo Group Ltd | Chemical compounds |
| JP3077047B2 (ja) | 1993-04-16 | 2000-08-14 | 参天製薬株式会社 | 新規ピペラジン誘導体 |
| AU2622595A (en) | 1994-06-03 | 1996-01-04 | John Wyeth & Brother Limited | Novel processes and intermediates for the preparation of piperazine derivatives |
| GB9411099D0 (en) | 1994-06-03 | 1994-07-27 | Wyeth John & Brother Ltd | Piperazine derivatives |
| GB9413772D0 (en) | 1994-07-08 | 1994-08-24 | Wyeth John & Brother Ltd | 5-HT1A ligands |
| EP0775118B1 (en) * | 1994-08-05 | 2003-06-04 | Pfizer Inc. | Benzimidazole derivatives having dopaminergic activity |
| US5681958A (en) * | 1995-06-07 | 1997-10-28 | Shaman Pharmaceuticals, Inc. | Cryptolepine analogs with hypoglycemic activity |
| US5889010A (en) * | 1995-05-18 | 1999-03-30 | Pfizer Inc. | Benzimidazole derivatives having dopaminergic activity |
| GB9514901D0 (en) | 1995-07-20 | 1995-09-20 | American Home Prod | Piperazine derivatives |
| ATE227268T1 (de) | 1996-04-10 | 2002-11-15 | Merck & Co Inc | Alpha v beta 3 antagonisten |
| US6271234B1 (en) | 1997-08-01 | 2001-08-07 | Recordati S.A., Chemical And Pharmaceutical Company | 1,4-disubstituted piperazines |
| JPH11106381A (ja) * | 1997-09-30 | 1999-04-20 | Ss Pharmaceut Co Ltd | クロメン誘導体及びその塩並びにこれを含有する医薬 |
| US6469007B2 (en) | 2000-11-28 | 2002-10-22 | Wyeth | Serotonergic agents |
| JP4429724B2 (ja) * | 2001-11-30 | 2010-03-10 | シェーリング コーポレイション | ［１，２，４］−トリアゾール二環式アデノシンＡ２ａレセプタアンタゴニスト |
| ES2334836T3 (es) | 2002-03-12 | 2010-03-16 | Wyeth | Preparacion de 2-((2,3-dihidro-benzo(1,4)dioxin-5-il)-(2-hidroxietil)-amino)-etanol y productos intermedios correspondientes. |
| US7361773B2 (en) * | 2002-03-12 | 2008-04-22 | Wyeth | Preparation of N1-(2'-pyridyl)-1,2-propanediamine sulfamic acid and its use in the synthesis of biologically active piperazines |
| CN1304388C (zh) * | 2002-03-12 | 2007-03-14 | 惠氏公司 | 合成手性n－芳基哌嗪的方法 |
| US7091349B2 (en) * | 2002-03-12 | 2006-08-15 | Wyeth | Process for synthesizing N-aryl piperazines with chiral N′-1-[benzoyl(2-pyridyl)amino]-2-propane substitution |
| CN101492383A (zh) * | 2002-03-12 | 2009-07-29 | 惠氏公司 | 制备手性1,4-二取代哌嗪的方法 |
-
2003
- 2003-03-10 CN CNA2008101786904A patent/CN101492383A/zh not_active Withdrawn
- 2003-03-10 EP EP03716403A patent/EP1483256A2/en not_active Withdrawn
- 2003-03-10 RU RU2004130313/04A patent/RU2315044C2/ru not_active IP Right Cessation
- 2003-03-10 AU AU2003220110A patent/AU2003220110B2/en not_active Expired - Fee Related
- 2003-03-10 WO PCT/US2003/007176 patent/WO2003078420A2/en active Application Filing
- 2003-03-10 KR KR10-2004-7014163A patent/KR20040091119A/ko not_active Application Discontinuation
- 2003-03-10 NZ NZ535169A patent/NZ535169A/xx unknown
- 2003-03-10 US US10/384,837 patent/US7019137B2/en not_active Expired - Fee Related
- 2003-03-10 MX MXPA04008730A patent/MXPA04008730A/es active IP Right Grant
- 2003-03-10 TW TW092105096A patent/TW200304825A/zh unknown
- 2003-03-10 IL IL16382803A patent/IL163828A0/xx unknown
- 2003-03-10 JP JP2003576425A patent/JP2005527530A/ja active Pending
- 2003-03-10 CA CA002477906A patent/CA2477906A1/en not_active Withdrawn
- 2003-03-10 BR BR0308347-0A patent/BR0308347A/pt not_active IP Right Cessation
- 2003-03-10 CN CNB038059169A patent/CN100451014C/zh not_active Expired - Fee Related
- 2003-03-11 AR ARP030100832A patent/AR038931A1/es unknown
- 2003-10-03 UA UA20041008215A patent/UA79774C2/uk unknown
-
2004
- 2004-08-24 CR CR7428A patent/CR7428A/es not_active Application Discontinuation
- 2004-09-10 EC EC2004005292A patent/ECSP045292A/es unknown
- 2004-09-23 NO NO20043988A patent/NO20043988L/no not_active Application Discontinuation
- 2004-10-11 ZA ZA200408205A patent/ZA200408205B/en unknown
-
2005
- 2005-06-07 US US11/147,055 patent/US7256289B2/en not_active Expired - Fee Related
-
2007
- 2007-07-06 RU RU2007125687/04A patent/RU2007125687A/ru not_active Application Discontinuation
- 2007-08-08 US US11/891,062 patent/US20080058543A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN100451014C (zh) | 2009-01-14 |
| WO2003078420A3 (en) | 2004-03-11 |
| IL163828A0 (en) | 2005-12-18 |
| AU2003220110A1 (en) | 2003-09-29 |
| CN1642937A (zh) | 2005-07-20 |
| RU2004130313A (ru) | 2005-04-10 |
| NZ535169A (en) | 2006-03-31 |
| US20080058543A1 (en) | 2008-03-06 |
| ECSP045292A (es) | 2004-10-26 |
| CN101492383A (zh) | 2009-07-29 |
| US20030208075A1 (en) | 2003-11-06 |
| TW200304825A (en) | 2003-10-16 |
| CR7428A (es) | 2008-09-23 |
| RU2315044C2 (ru) | 2008-01-20 |
| EP1483256A2 (en) | 2004-12-08 |
| US7019137B2 (en) | 2006-03-28 |
| MXPA04008730A (es) | 2004-12-06 |
| KR20040091119A (ko) | 2004-10-27 |
| BR0308347A (pt) | 2005-01-25 |
| CA2477906A1 (en) | 2003-09-25 |
| NO20043988L (no) | 2004-09-23 |
| US7256289B2 (en) | 2007-08-14 |
| RU2007125687A (ru) | 2009-01-20 |
| WO2003078420A2 (en) | 2003-09-25 |
| US20050228181A1 (en) | 2005-10-13 |
| JP2005527530A (ja) | 2005-09-15 |
| ZA200408205B (en) | 2007-03-28 |
| AR038931A1 (es) | 2005-02-02 |
| AU2003220110B2 (en) | 2009-04-09 |
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