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 PDF

Info

Publication number: UA79774C2
Authority: UA; Ukraine
Prior art keywords: compound; formula; benzodioxin; dihydro; group
Prior art date: 2002-03-12

Application number

UA20041008215A

Other languages

English (en)

Ukrainian (uk)

Inventor

Ivo Jirkovsky

Joseph Zeldis

Gregg Brian Feigelson

Original Assignee

Wyeth Corp

Priority date (The priority date 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 date listed.)

2002-03-12

Filing date

2003-10-03

Publication date

2007-07-25

2003-10-03 Application filed by Wyeth Corp filed Critical Wyeth Corp

2007-07-25 Publication of UA79774C2 publication Critical patent/UA79774C2/uk

Links

-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)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (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)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (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)

UA20041008215A 2002-03-12 2003-10-03 Process for preparation of chiral 1,4-disubstituted piperazines, intermediate (variants) UA79774C2 (en)

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 (de)
EP (1)	EP1483256A2 (de)
JP (1)	JP2005527530A (de)
KR (1)	KR20040091119A (de)
CN (2)	CN100451014C (de)
AR (1)	AR038931A1 (de)
AU (1)	AU2003220110B2 (de)
BR (1)	BR0308347A (de)
CA (1)	CA2477906A1 (de)
CR (1)	CR7428A (de)
EC (1)	ECSP045292A (de)
IL (1)	IL163828A0 (de)
MX (1)	MXPA04008730A (de)
NO (1)	NO20043988L (de)
NZ (1)	NZ535169A (de)
RU (2)	RU2315044C2 (de)
TW (1)	TW200304825A (de)
UA (1)	UA79774C2 (de)
WO (1)	WO2003078420A2 (de)
ZA (1)	ZA200408205B (de)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7504395B2 (en) *	2001-07-20	2009-03-17	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
MXPA04008730A (es) *	2002-03-12	2004-12-06	Wyeth Corp	Proceso para preparacion de piperazinas quirales 1,4-disustituidas.
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
US20050209245A1 (en) *	2004-03-19	2005-09-22	Wyeth	Process for preparing N-aryl-piperazine derivatives
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 (26)

* Cited by examiner, † Cited by third party
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
NZ209876A (en) *	1983-10-17	1988-03-30	Duphar Int Res	Piperazines and pharmaceutical compositions
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	Piperazine derivatives their preparation and pharmaceutical compositions containing them
GB9125900D0 (en) *	1991-12-05	1992-02-05	Wyeth John & Brother Ltd	Piperazine derivatives
IL105348A0 (en) *	1992-04-13	1993-08-18	Fujisawa Pharmaceutical Co	Azabicyclo derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same
GB9208740D0 (en) *	1992-04-23	1992-06-10	Glaxo Group Ltd	Chemical compounds
WO1994024115A1 (fr)	1993-04-16	1994-10-27	Santen Pharmaceutical Co., Ltd.	Nouveau derive de piperazine
GB9411099D0 (en)	1994-06-03	1994-07-27	Wyeth John & Brother Ltd	Piperazine derivatives
EP0763024B1 (de)	1994-06-03	2002-08-14	JOHN WYETH & BROTHER LIMITED	Verfahren und zwischenprodukte zur herstellung von piperazinderivaten
GB9413772D0 (en)	1994-07-08	1994-08-24	Wyeth John & Brother Ltd	5-HT1A ligands
DK0775118T3 (da) *	1994-08-05	2003-09-29	Pfizer	Benzimidazolderivater, der har dopaminerg aktivitet
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
CA2251017A1 (en)	1996-04-10	1997-10-16	Mark E. Duggan	.alpha.v.beta.3 antagonists
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
ES2283625T3 (es) *	2001-11-30	2007-11-01	Schering Corporation	Antagonistas del receptopr a2a de adenosina de (1,2,4)-triazol biciclicos.
ATE439356T1 (de) *	2002-03-12	2009-08-15	Wyeth Corp	Verfahren zur herstellung von chiralen n-aryl piperazinen
MXPA04008730A (es)	2002-03-12	2004-12-06	Wyeth Corp	Proceso para preparacion de piperazinas quirales 1,4-disustituidas.
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
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
ATE360002T1 (de)	2002-03-12	2007-05-15	Wyeth Corp	Verfahren zur herstellung von n1-(2'-pyridyl)-1,2-propandiaminsulfamidsäure und ihre verwendung zur herstellung von biologisch aktiven piperazinen

2003
- 2003-03-10 MX MXPA04008730A patent/MXPA04008730A/es active IP Right Grant
- 2003-03-10 AU AU2003220110A patent/AU2003220110B2/en not_active Expired - Fee Related
- 2003-03-10 EP EP03716403A patent/EP1483256A2/de not_active Withdrawn
- 2003-03-10 TW TW092105096A patent/TW200304825A/zh unknown
- 2003-03-10 IL IL16382803A patent/IL163828A0/xx unknown
- 2003-03-10 RU RU2004130313/04A patent/RU2315044C2/ru not_active IP Right Cessation
- 2003-03-10 NZ NZ535169A patent/NZ535169A/xx unknown
- 2003-03-10 CA CA002477906A patent/CA2477906A1/en not_active Withdrawn
- 2003-03-10 JP JP2003576425A patent/JP2005527530A/ja active Pending
- 2003-03-10 KR KR10-2004-7014163A patent/KR20040091119A/ko not_active Ceased
- 2003-03-10 WO PCT/US2003/007176 patent/WO2003078420A2/en not_active Ceased
- 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
- 2003-03-10 CN CNA2008101786904A patent/CN101492383A/zh not_active Withdrawn
- 2003-03-10 US US10/384,837 patent/US7019137B2/en 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
ECSP045292A (es)	2004-10-26
CN101492383A (zh)	2009-07-29
WO2003078420A3 (en)	2004-03-11
CN100451014C (zh)	2009-01-14
NZ535169A (en)	2006-03-31
RU2007125687A (ru)	2009-01-20
TW200304825A (en)	2003-10-16
JP2005527530A (ja)	2005-09-15
CR7428A (es)	2008-09-23
US20030208075A1 (en)	2003-11-06
WO2003078420A2 (en)	2003-09-25
CA2477906A1 (en)	2003-09-25
EP1483256A2 (de)	2004-12-08
AU2003220110A1 (en)	2003-09-29
BR0308347A (pt)	2005-01-25
RU2004130313A (ru)	2005-04-10
US20050228181A1 (en)	2005-10-13
AU2003220110B2 (en)	2009-04-09
MXPA04008730A (es)	2004-12-06
IL163828A0 (en)	2005-12-18
US7256289B2 (en)	2007-08-14
NO20043988L (no)	2004-09-23
US7019137B2 (en)	2006-03-28
CN1642937A (zh)	2005-07-20
RU2315044C2 (ru)	2008-01-20
ZA200408205B (en)	2007-03-28
KR20040091119A (ko)	2004-10-27
US20080058543A1 (en)	2008-03-06
AR038931A1 (es)	2005-02-02

Publication	Publication Date	Title
EP4043468B1 (de)	2025-07-16	Verfahren zur herstellung von glufosinat
JP2020510630A (ja)	2020-04-09	Ｗｅｅ１阻害剤としての１，２−ジヒドロ−３Ｈ−ピラゾロ［３，４−ｄ］ピリミジン−３−オン誘導体
KR20190025990A (ko)	2019-03-12	4-알콕시-3-(아실 또는 알킬)옥시피콜린아미드의 제조 방법
US20080058543A1 (en)	2008-03-06	Process for making chiral 1,4-disubstituted piperazines
RU2315762C2 (ru)	2008-01-27	Способ синтеза хиральных n-арилпиперазинов
RU2314294C2 (ru)	2008-01-10	Способы получения производных пиперазина и промежуточное вещество
WO2014068341A2 (en)	2014-05-08	Chiral fluorinating reagents
EP0323881B1 (de)	1993-03-31	Cyano-Diene, Halopyridine, Zwischenverbindungen und ein Verfahren zu deren Herstellung
JP2018534248A (ja)	2018-11-22	立体選択的方法
WO2010012797A2 (en)	2010-02-04	Synthesis of 3,4-diaryl-4,5-dihydro-(1h)-pyrazole-1- carboxamidine derivatives
SU1299507A3 (ru)	1987-03-23	Способ получени производных фторметилхинолина
JPH09221472A (ja)	1997-08-26	α−シクロアルキルアルキル置換メタンアミン類の不斉合成方法
JP4922157B2 (ja)	2012-04-25	ベンゾオキサチエピンの合成方法とその中間体
US9481645B2 (en)	2016-11-01	Composition, synthesis, and use of a new class of isonitriles
SU1318587A1 (ru)	1987-06-23	Способ получени @ , @ -дизамещенных 1,8-диаминонафталинов
KR20240006335A (ko)	2024-01-15	젖산 제조 방법
SU523642A3 (ru)	1976-07-30	Способ получени производных трифенилфосфина
SU354656A1 (de)
JPS5825663B2 (ja)	1983-05-28	グアニジノカプロン酸エステルの製法
WO1998045264A1 (en)	1998-10-15	Process for producing piperidinecarboxylic acid amides
JPWO1993025532A1 (ja)	1994-07-07	カルボン酸誘導体及び製法
JP2005330187A (ja)	2005-12-02	１−（ニトロアリール）アルキルアミンの製造方法
PL159216B1 (en)	1992-11-30	Method of manufacture of arylsulfonalcane acids