CA2535728C - Preparation de risperidone - Google Patents

Preparation de risperidone Download PDF

Info

Publication number: CA2535728C
Authority: CA; Canada
Prior art keywords: risperidone; present; risperidone form; isopropanol; filtered
Prior art date: 2000-08-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA002535728A

Other languages

English (en)

Other versions

CA2535728A1 (fr

Inventor

Barnaba Krochmal

Dov Diller

Ben-Zion Dolitzky

Judith Aronhime

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Teva Pharmaceutical Industries Ltd

Original Assignee

Teva Pharmaceutical Industries Ltd

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.)

2000-08-14

Filing date

2001-08-14

Publication date

2006-10-03

2001-08-14 Application filed by Teva Pharmaceutical Industries Ltd filed Critical Teva Pharmaceutical Industries Ltd

2001-08-14 Priority claimed from CA002419314A external-priority patent/CA2419314C/fr

2002-02-21 Publication of CA2535728A1 publication Critical patent/CA2535728A1/fr

2006-10-03 Application granted granted Critical

2006-10-03 Publication of CA2535728C publication Critical patent/CA2535728C/fr

2021-08-14 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 title claims abstract description 193
229960001534 risperidone Drugs 0.000 title claims abstract description 193
238000002360 preparation method Methods 0.000 title description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
238000000634 powder X-ray diffraction Methods 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
238000001556 precipitation Methods 0.000 claims description 19
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 8
229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
239000007864 aqueous solution Substances 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
235000017550 sodium carbonate Nutrition 0.000 claims 1
238000000034 method Methods 0.000 abstract description 44
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 62
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 25
239000002904 solvent Substances 0.000 description 25
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 20
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
238000010438 heat treatment Methods 0.000 description 15
239000000243 solution Substances 0.000 description 15
150000001875 compounds Chemical class 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
239000006185 dispersion Substances 0.000 description 10
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 10
238000003786 synthesis reaction Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
239000000725 suspension Substances 0.000 description 8
239000012065 filter cake Substances 0.000 description 7
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
239000000463 material Substances 0.000 description 6
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 5
238000009835 boiling Methods 0.000 description 5
-1 for example Chemical compound 0.000 description 5
150000002576 ketones Chemical class 0.000 description 5
239000000843 powder Substances 0.000 description 5
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000004090 dissolution Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000002441 X-ray diffraction Methods 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical class [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
239000002002 slurry Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
CMWCQQUYLPYOMY-UHFFFAOYSA-N 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound C1CCCN2C(=O)C(CCCl)=C(C)N=C21 CMWCQQUYLPYOMY-UHFFFAOYSA-N 0.000 description 1
WDNMHZRFIIOXOD-UHFFFAOYSA-N 3-[2-[4-(6-fluoro-2,3-dihydro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound N1OC2=CC(F)=CC=C2C1C(CC1)CCN1CCC(C1=O)=C(C)N=C2N1CCCC2 WDNMHZRFIIOXOD-UHFFFAOYSA-N 0.000 description 1
LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
238000004566 IR spectroscopy Methods 0.000 description 1
101100281518 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) fox-2 gene Proteins 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
JBPUGFODGPKTDW-SFHVURJKSA-N [(3s)-oxolan-3-yl] n-[[3-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoylamino]phenyl]methyl]carbamate Chemical compound C=1C=C(C=2OC=NC=2)C(OC)=CC=1NC(=O)NC(C=1)=CC=CC=1CNC(=O)O[C@H]1CCOC1 JBPUGFODGPKTDW-SFHVURJKSA-N 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
150000008316 benzisoxazoles Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000001938 differential scanning calorimetry curve Methods 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000002547 new drug Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
238000001144 powder X-ray diffraction data Methods 0.000 description 1
239000000047 product Substances 0.000 description 1
230000011514 reflex Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000001757 thermogravimetry curve Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA002535728A 2000-08-14 2001-08-14 Preparation de risperidone Expired - Fee Related CA2535728C (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US22536100P	2000-08-14	2000-08-14
US60/225,361		2000-08-14
US24326300P	2000-10-25	2000-10-25
US60/243,263		2000-10-25
CA002419314A CA2419314C (fr)	2000-08-14	2001-08-14	Preparation de risperidone

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002419314A Division CA2419314C (fr)	2000-08-14	2001-08-14	Preparation de risperidone

Publications (2)

Publication Number	Publication Date
CA2535728A1 CA2535728A1 (fr)	2002-02-21
CA2535728C true CA2535728C (fr)	2006-10-03

Family

ID=36283175

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
CA002549244A Abandoned CA2549244A1 (fr)	2000-08-14	2001-08-14	Preparation de risperidone
CA002535742A Expired - Fee Related CA2535742C (fr)	2000-08-14	2001-08-14	Preparation de risperidone
CA002535728A Expired - Fee Related CA2535728C (fr)	2000-08-14	2001-08-14	Preparation de risperidone

Family Applications Before (2)

Application Number	Title	Priority Date	Filing Date
CA002549244A Abandoned CA2549244A1 (fr)	2000-08-14	2001-08-14	Preparation de risperidone
CA002535742A Expired - Fee Related CA2535742C (fr)	2000-08-14	2001-08-14	Preparation de risperidone

Country Status (1)

Country	Link
CA (3)	CA2549244A1 (fr)

2001
- 2001-08-14 CA CA002549244A patent/CA2549244A1/fr not_active Abandoned
- 2001-08-14 CA CA002535742A patent/CA2535742C/fr not_active Expired - Fee Related
- 2001-08-14 CA CA002535728A patent/CA2535728C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2535728A1 (fr)	2002-02-21
CA2535742A1 (fr)	2002-02-21
CA2535742C (fr)	2006-10-10
CA2549244A1 (fr)	2002-02-21

Legal Events

Date	Code	Title	Description
2006-02-23	EEER	Examination request
2011-08-15	MKLA	Lapsed
2023-10-17	MKLA	Lapsed	Effective date: 20110815

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