SK2542004A3 - Improved process for the preparation of 3-{2-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2- methyl-4H-pyrido[1,2-alpha]pyrimidin-4-one - Google Patents

Improved process for the preparation of 3-{2-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2- methyl-4H-pyrido[1,2-alpha]pyrimidin-4-one Download PDF

Info

Publication number: SK2542004A3
Authority: SK; Slovakia
Prior art keywords: formula; methyl; oxime; acid addition; tetrahydro
Prior art date: 2001-11-13

Application number

SK254-2004A

Other languages

English (en)

Slovak (sk)

Inventor

Laszlo Pongo

Jozsef Reiter

Gyula Simig

Gabor Berecz

Gyorgy Clementis

Peter Slegel

Janos Szulagyi

Laszlo Koncz

Donath Gyorgyi Vereczkeyne

Kalman Nagy

Gyulane Kortvelyessy

Original Assignee

Egyt Gyogyszervegyeszeti Gyar

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.)

2001-11-13

Filing date

2002-11-13

Publication date

2004-12-01

2002-11-13 Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar

2004-12-01 Publication of SK2542004A3 publication Critical patent/SK2542004A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 31
238000002360 preparation method Methods 0.000 title claims abstract description 25
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 title claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title description 16
-1 piperidine oxime Chemical class 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 17
239000002253 acid Substances 0.000 claims abstract description 16
150000002923 oximes Chemical class 0.000 claims abstract description 15
239000002585 base Substances 0.000 claims abstract description 14
229910052736 halogen Inorganic materials 0.000 claims abstract description 11
150000002367 halogens Chemical class 0.000 claims abstract description 11
239000003513 alkali Substances 0.000 claims abstract description 8
238000006798 ring closing metathesis reaction Methods 0.000 claims abstract description 8
239000012442 inert solvent Substances 0.000 claims abstract description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 5
229910001854 alkali hydroxide Inorganic materials 0.000 claims abstract description 5
150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 5
150000004703 alkoxides Chemical class 0.000 claims abstract description 4
239000003960 organic solvent Substances 0.000 claims abstract description 4
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
238000006243 chemical reaction Methods 0.000 claims description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
239000012458 free base Substances 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
229910052801 chlorine Inorganic materials 0.000 claims 1
239000000460 chlorine Substances 0.000 claims 1
RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 abstract description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 23
150000001875 compounds Chemical class 0.000 description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
229960001534 risperidone Drugs 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
239000000539 dimer Substances 0.000 description 8
238000009835 boiling Methods 0.000 description 7
230000000052 comparative effect Effects 0.000 description 7
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000000203 mixture Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
150000008316 benzisoxazoles Chemical class 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 4
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002904 solvent Substances 0.000 description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
239000003480 eluent Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
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 description 3
125000006334 2,4-difluoro benzoyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(F)C([H])=C1F 0.000 description 2
BRCINVRBDDVLDW-UHFFFAOYSA-N 3-[2-[4-[c-(2,4-difluorophenyl)-n-hydroxycarbonimidoyl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound CC=1N=C2CCCCN2C(=O)C=1CCN(CC1)CCC1C(=NO)C1=CC=C(F)C=C1F BRCINVRBDDVLDW-UHFFFAOYSA-N 0.000 description 2
MRMGJMGHPJZSAE-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C1CCNCC1 MRMGJMGHPJZSAE-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000000356 contaminant Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
239000012535 impurity Substances 0.000 description 2
CPVWKXXFKMUDPA-UHFFFAOYSA-N n-[(2,4-difluorophenyl)-piperidin-4-ylmethylidene]hydroxylamine;hydrochloride Chemical compound Cl.C=1C=C(F)C=C(F)C=1C(=NO)C1CCNCC1 CPVWKXXFKMUDPA-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
229920006395 saturated elastomer Polymers 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
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
QPJONRGTWKXJLG-UHFFFAOYSA-N (2,4-difluorophenyl)-piperidin-4-ylmethanone;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(=O)C1CCNCC1 QPJONRGTWKXJLG-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000005594 diketone group Chemical group 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
ZUNVFGNAQYZBGO-UHFFFAOYSA-N n-(2,3,4,5-tetrahydropyridin-6-yl)hydroxylamine Chemical class ONC1=NCCCC1 ZUNVFGNAQYZBGO-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
XESLSYPFOYZAPG-UHFFFAOYSA-N piperidin-1-ium-2-one;chloride Chemical class Cl.O=C1CCCCN1 XESLSYPFOYZAPG-UHFFFAOYSA-N 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK254-2004A 2001-11-13 2002-11-13 Improved process for the preparation of 3-{2-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2- methyl-4H-pyrido[1,2-alpha]pyrimidin-4-one SK2542004A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU0104873A HU227118B1 (en)	2001-11-13	2001-11-13	Process for the preparation of 3-{2-[4-(6-fluoro-1,2-benzizoxazol-3-yl)-1-piperidinyl]-ethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido[1,2-a]pyrimidin-4-one
PCT/HU2002/000120 WO2003042212A1 (en)	2001-11-13	2002-11-13	Improved process for the preparation of 3-{2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido[1,2-a]pyrimidin-4-one

Publications (1)

Publication Number	Publication Date
SK2542004A3 true SK2542004A3 (en)	2004-12-01

Family

ID=89979882

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK254-2004A SK2542004A3 (en)	2001-11-13	2002-11-13	Improved process for the preparation of 3-{2-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2- methyl-4H-pyrido[1,2-alpha]pyrimidin-4-one

Country Status (14)

Country	Link
US (1)	US7307168B2 (cs)
EP (1)	EP1461338B1 (cs)
JP (1)	JP4297785B2 (cs)
AT (1)	ATE361298T1 (cs)
BG (1)	BG108757A (cs)
CZ (1)	CZ2004698A3 (cs)
DE (1)	DE60219957T8 (cs)
DK (1)	DK1461338T3 (cs)
ES (1)	ES2286332T3 (cs)
HU (1)	HU227118B1 (cs)
PL (1)	PL369233A1 (cs)
PT (1)	PT1461338E (cs)
SK (1)	SK2542004A3 (cs)
WO (1)	WO2003042212A1 (cs)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2004009591A1 (en) *	2002-07-22	2004-01-29	Aurobindo Pharma Ltd.	A process for the preparation of antipsychotic risperidone
CN100390146C (zh)	2002-11-13	2008-05-28	斯索恩有限公司	制备利培酮的方法和用于该方法的中间体
HUP0401379A3 (en) *	2004-07-08	2006-04-28	Richter Gedeon Vegyeszet	Process for the preparation of risperidon
HUP0402163A2 (en) *	2004-10-25	2006-05-29	Richter Gedeon Vegyeszet	Process for the preparation of risperidone
HUP0600555A3 (en) *	2006-07-03	2008-10-28	Egis Gyogyszergyar Nyrt	Use of 4-chloro-5-{2-[4-(6-fluoro-1,2-benz[d]izoxazol-3-yl)piperidin-1-yl]ethylamino}2-methyl-3(2h)-piridazinon for the production of pharmaceutical compositions for influencing cognitive functions and causing neuroprotective effect
CN112624992B (zh) *	2021-01-19	2026-01-02	浙江华海药业股份有限公司	一种6-氟-3-（4-哌啶基）-1,2-苯并异噁唑盐酸盐的纯化方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4804663A (en) *	1985-03-27	1989-02-14	Janssen Pharmaceutica N.V.	3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
GB9008850D0 (en) *	1990-04-19	1990-06-13	Janssen Pharmaceutica Nv	Novel 2,9-disubstituted-4h-pyridol(1,2-a)pyrimidin-4-ones
ES2085234B1 (es) *	1994-02-24	1997-01-16	Vita Invest Sa	Agente activo sobre el sistema nervioso central, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen.
DE60009959T2 (de) *	2000-05-05	2005-03-31	Rpg Life Sciences Limited	Verfahren zur herstellung von antipsychotischem 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4h-pyrido[1,2-a]pyrimidin-4-on

2001
- 2001-11-13 HU HU0104873A patent/HU227118B1/hu not_active IP Right Cessation
2002
- 2002-11-13 PL PL02369233A patent/PL369233A1/xx not_active Application Discontinuation
- 2002-11-13 DE DE60219957T patent/DE60219957T8/de active Active
- 2002-11-13 DK DK02803068T patent/DK1461338T3/da active
- 2002-11-13 PT PT02803068T patent/PT1461338E/pt unknown
- 2002-11-13 EP EP02803068A patent/EP1461338B1/en not_active Expired - Lifetime
- 2002-11-13 CZ CZ2004698A patent/CZ2004698A3/cs unknown
- 2002-11-13 AT AT02803068T patent/ATE361298T1/de active
- 2002-11-13 US US10/495,362 patent/US7307168B2/en not_active Expired - Fee Related
- 2002-11-13 WO PCT/HU2002/000120 patent/WO2003042212A1/en not_active Ceased
- 2002-11-13 SK SK254-2004A patent/SK2542004A3/sk unknown
- 2002-11-13 ES ES02803068T patent/ES2286332T3/es not_active Expired - Lifetime
- 2002-11-13 JP JP2003544048A patent/JP4297785B2/ja not_active Expired - Fee Related
2004
- 2004-06-11 BG BG108757A patent/BG108757A/bg unknown

Also Published As

Publication number	Publication date
BG108757A (bg)	2005-03-31
JP2005513019A (ja)	2005-05-12
ATE361298T1 (de)	2007-05-15
DE60219957D1 (de)	2007-06-14
DE60219957T8 (de)	2008-04-24
HU0104873D0 (en)	2002-01-28
US20050004141A1 (en)	2005-01-06
US7307168B2 (en)	2007-12-11
WO2003042212A1 (en)	2003-05-22
HUP0104873A2 (hu)	2003-08-28
JP4297785B2 (ja)	2009-07-15
ES2286332T3 (es)	2007-12-01
CZ2004698A3 (cs)	2004-09-15
EP1461338A1 (en)	2004-09-29
EP1461338B1 (en)	2007-05-02
DK1461338T3 (da)	2007-09-03
DE60219957T2 (de)	2008-01-17
HU227118B1 (en)	2010-07-28
PL369233A1 (en)	2005-04-18
HUP0104873A3 (en)	2003-11-28
PT1461338E (pt)	2007-07-23

Legal Events

Date	Code	Title	Description
2012-04-03	FD9A	Suspended procedure due to non-payment of fee

Publication	Publication Date	Title
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US20080114007A1 (en)	2008-05-15	5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase
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AU2005257496B2 (en)	2011-01-06	Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with a cyclic amino group as CRF antagonists
JP6426185B2 (ja)	2018-11-21	Ｔｎｆ活性のモジュレーターとしてのトリアゾロピリジン誘導体
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ES2367312T3 (es)	2011-11-02	DERIVADOS DE PIRROLO [3,2-c] PIRIDINA Y PROCESOS PARA LA PREPARACIÓN DE LOS MISMOS.
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