LV13441B - A method for the preparation of enantiomercally pure mirtazapine - Google Patents

A method for the preparation of enantiomercally pure mirtazapine Download PDF

Info

Publication number: LV13441B
Authority: LV; Latvia
Prior art keywords: acid; combination; solvent; compound; mirtazapine
Prior art date: 2003-07-10

Application number

LVP-06-21A

Other languages

English (en)

Latvian (lv)

Inventor

Johannes Hubertus Wieringa

De Ven Adrianus Antonius M Van

Gerardus Johannes Kemperman

Original Assignee

Organon Nv

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.)

2003-07-10

Filing date

2006-02-10

Publication date

2006-08-20

2006-02-10 Application filed by Organon Nv filed Critical Organon Nv

2006-08-20 Publication of LV13441B publication Critical patent/LV13441B/en

Links

238000000034 method Methods 0.000 title claims abstract description 46
RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 title claims abstract description 42
229960001785 mirtazapine Drugs 0.000 title claims abstract description 41
238000002360 preparation method Methods 0.000 title claims abstract description 15
239000002253 acid Substances 0.000 claims abstract description 76
150000001875 compounds Chemical class 0.000 claims abstract description 44
239000002904 solvent Substances 0.000 claims abstract description 31
239000003960 organic solvent Substances 0.000 claims abstract description 16
238000006243 chemical reaction Methods 0.000 claims description 24
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 20
229920000137 polyphosphoric acid Polymers 0.000 claims description 20
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
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 claims description 8
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
238000007363 ring formation reaction Methods 0.000 claims description 6
229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
239000011707 mineral Substances 0.000 claims description 3
230000000707 stereoselective effect Effects 0.000 claims description 3
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 claims 1
238000006798 ring closing metathesis reaction Methods 0.000 abstract description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
239000000203 mixture Substances 0.000 description 7
150000003839 salts Chemical class 0.000 description 7
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000012044 organic layer Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
PYZPABZGIRHQTA-MRXNPFEDSA-N [2-[(2s)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl]methanol Chemical compound C1([C@@H]2N(CCN(C2)C)C=2C(=CC=CN=2)CO)=CC=CC=C1 PYZPABZGIRHQTA-MRXNPFEDSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
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 3
-1 O’Connor and Leonard Chemical compound 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
239000012453 solvate Substances 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
RONZAEMNMFQXRA-MRXNPFEDSA-N esmirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)C[C@@H]2C2=CC=CC=C21 RONZAEMNMFQXRA-MRXNPFEDSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
XDJWZONZDVNKDU-UHFFFAOYSA-N 1314-24-5 Chemical compound O=POP=O XDJWZONZDVNKDU-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
RIMRLBGNCLMSNH-UHFFFAOYSA-N 2-phenylpiperazine Chemical compound C1NCCNC1C1=CC=CC=C1 RIMRLBGNCLMSNH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
208000020401 Depressive disease Diseases 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
RONZAEMNMFQXRA-INIZCTEOSA-N LSM-5894 Chemical compound C1C2=CC=CN=C2N2CCN(C)C[C@H]2C2=CC=CC=C21 RONZAEMNMFQXRA-INIZCTEOSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
OQIQSTLJSLGHID-WNWIJWBNSA-N aflatoxin B1 Chemical compound C=1([C@@H]2C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O OQIQSTLJSLGHID-WNWIJWBNSA-N 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
VMPVEPPRYRXYNP-UHFFFAOYSA-I antimony(5+);pentachloride Chemical compound Cl[Sb](Cl)(Cl)(Cl)Cl VMPVEPPRYRXYNP-UHFFFAOYSA-I 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
150000007942 carboxylates Chemical group 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
230000006698 induction Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
VSAISIQCTGDGPU-UHFFFAOYSA-N phosphorus trioxide Inorganic materials O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
201000002859 sleep apnea Diseases 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- 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
- A61P25/24—Antidepressants
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

LVP-06-21A 2003-07-10 2006-02-10 A method for the preparation of enantiomercally pure mirtazapine LV13441B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP03102095		2003-07-10

Publications (1)

Publication Number	Publication Date
LV13441B true LV13441B (en)	2006-08-20

Family

ID=34042934

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LVP-06-21A LV13441B (en)	2003-07-10	2006-02-10	A method for the preparation of enantiomercally pure mirtazapine

Country Status (35)

Country	Link
US (2)	US8058436B2 (fr)
EP (1)	EP1656365B1 (fr)
JP (1)	JP4668184B2 (fr)
KR (1)	KR20060056315A (fr)
CN (1)	CN100558722C (fr)
AR (1)	AR046494A1 (fr)
AT (1)	ATE433965T1 (fr)
AU (1)	AU2004255874B2 (fr)
BR (1)	BRPI0412447A (fr)
CA (1)	CA2531165C (fr)
CO (1)	CO5640123A2 (fr)
CY (1)	CY1109327T1 (fr)
DE (1)	DE602004021605D1 (fr)
DK (1)	DK1656365T3 (fr)
EC (1)	ECSP066271A (fr)
ES (1)	ES2327123T3 (fr)
HR (1)	HRP20051019A2 (fr)
IL (1)	IL172549A0 (fr)
IS (1)	IS2674B (fr)
LT (1)	LT5382B (fr)
LV (1)	LV13441B (fr)
MX (1)	MXPA06000325A (fr)
NO (1)	NO20056175L (fr)
NZ (1)	NZ544360A (fr)
PE (1)	PE20050323A1 (fr)
PL (1)	PL1656365T3 (fr)
PT (1)	PT1656365E (fr)
RS (1)	RS20050972A (fr)
RU (1)	RU2352566C2 (fr)
SG (1)	SG144914A1 (fr)
SI (1)	SI1656365T1 (fr)
TW (1)	TWI335915B (fr)
UA (1)	UA83666C2 (fr)
WO (1)	WO2005005410A1 (fr)
ZA (1)	ZA200600019B (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP5080050B2 (ja) *	2005-09-26	2012-11-21	住友化学株式会社	光学活性なピペラジン化合物の製造方法
EP1930325A4 (fr) *	2005-09-26	2010-02-24	Sumitomo Chemical Co	Procédé de synthèse d'un dérivé de pipérazine optiquement actif
TW200808804A (en) *	2006-05-22	2008-02-16	Organon Nv	Mirtazapine for the treatment of neuropathic pain
TW200815370A (en) *	2006-06-16	2008-04-01	Organon Nv	Stereoselective synthesis of (S)-1-methyl-3-phenylpiperazine
JP5438976B2 (ja) *	2007-02-09	2014-03-12	株式会社カネカ	光学活性２−アリールピペラジン誘導体の製造法
JP5192707B2 (ja) *	2007-03-22	2013-05-08	住友化学株式会社	ミルタザピンの製造方法
WO2008125578A2 (fr)	2007-04-11	2008-10-23	N.V. Organon	Procédés de préparation d'un énantiomère d'une benzazépine tétracyclique
US7994314B2 (en)	2007-04-11	2011-08-09	N.V. Organon	Method for the preparation of an enantiomerically pure benzazepine
KR101485418B1 (ko) *	2013-05-29	2015-01-26	주식회사 메디켐코리아	고순도 미르타자핀의 제조방법
SI3261645T1 (sl)	2015-02-27	2021-08-31	Dechra Limited	Stimulacija apetita, uravnavanje izgube mase in zdravljenje anoreksije pri psih in mačkah
KR102540021B1 (ko) *	2020-12-02	2023-06-07	(주)유케이케미팜	대량 생산에 적합한 미르타자핀의 제조방법

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3959470A (en) *	1972-11-28	1976-05-25	Mikhail Davidovich Mashkovsky	Psychotropic medicinal preparation
NL189199C (nl) *	1975-04-05	1993-02-01	Akzo Nv	Werkwijze ter bereiding van farmaceutische preparaten met werking op het centraal zenuwstelsel op basis van benz(aryl)azepinederivaten, de verkregen gevormde farmaceutische preparaten, alsmede werkwijze ter bereiding van de toe te passen benz(aryl)azepinederivaten.
RU2048469C1 (ru) *	1989-10-05	1995-11-20	Санкио Компани Лимитед	Способ получения азетидинового производного или его фармацевтически приемлемой соли
CA2309744A1 (fr)	1997-11-14	1999-05-27	Akzo Nobel N.V.	Utilisation de la mirtazapine pour le traitement des apnees du sommeil
JPH11222407A (ja) *	1997-11-14	1999-08-17	Sankyo Co Ltd	新規殺菌剤
US20030069417A1 (en) *	1999-04-19	2003-04-10	Claude Singer	Novel synthesis and crystallization of piperazine ring-containing compounds
PL366289A1 (en)	1999-04-19	2005-01-24	Teva Pharmaceutical Industries Ltd.	Novel synthesis and crystallization of piperazine ring-containing compounds
US6068695A (en) *	1999-07-13	2000-05-30	Bayer Corporation	Process for the continuous preparation of quinacridones
AU6476300A (en)	1999-09-30	2001-05-10	Sumika Fine Chemicals Co., Ltd.	Process for the preparation of a piperazine derivative
WO2001042239A1 (fr)	1999-12-13	2001-06-14	Sumika Fine Chemicals Co., Ltd.	Procede de preparation d'un compose pyridinemethanol
KR20020069371A (ko)	2000-02-11	2002-08-30	악조 노벨 엔.브이.	수면 장애의 치료를 위한 미르타자핀의 용도
JP2001342188A (ja) *	2000-03-27	2001-12-11	Takeda Chem Ind Ltd	縮合ピラゾール誘導体、その製造法および用途
TW200538100A (en) *	2004-04-21	2005-12-01	Akzo Nobel Nv	Mirtazapine salts

2004
- 2004-05-07 UA UAA200600274A patent/UA83666C2/ru unknown
- 2004-06-28 TW TW093118845A patent/TWI335915B/zh not_active IP Right Cessation
- 2004-07-05 HR HR20051019A patent/HRP20051019A2/xx not_active Application Discontinuation
- 2004-07-05 NZ NZ544360A patent/NZ544360A/en not_active IP Right Cessation
- 2004-07-05 SI SI200431183T patent/SI1656365T1/sl unknown
- 2004-07-05 PT PT04741958T patent/PT1656365E/pt unknown
- 2004-07-05 MX MXPA06000325A patent/MXPA06000325A/es active IP Right Grant
- 2004-07-05 DK DK04741958T patent/DK1656365T3/da active
- 2004-07-05 CA CA2531165A patent/CA2531165C/fr not_active Expired - Fee Related
- 2004-07-05 DE DE602004021605T patent/DE602004021605D1/de not_active Expired - Lifetime
- 2004-07-05 SG SG200805127-8A patent/SG144914A1/en unknown
- 2004-07-05 AU AU2004255874A patent/AU2004255874B2/en not_active Expired
- 2004-07-05 EP EP04741958A patent/EP1656365B1/fr not_active Expired - Lifetime
- 2004-07-05 CN CNB2004800194891A patent/CN100558722C/zh not_active Expired - Lifetime
- 2004-07-05 US US10/564,193 patent/US8058436B2/en not_active Expired - Fee Related
- 2004-07-05 RS YUP-2005/0972A patent/RS20050972A/sr unknown
- 2004-07-05 WO PCT/EP2004/051357 patent/WO2005005410A1/fr not_active Ceased
- 2004-07-05 PL PL04741958T patent/PL1656365T3/pl unknown
- 2004-07-05 ES ES04741958T patent/ES2327123T3/es not_active Expired - Lifetime
- 2004-07-05 AT AT04741958T patent/ATE433965T1/de active
- 2004-07-05 KR KR1020067000511A patent/KR20060056315A/ko not_active Abandoned
- 2004-07-05 JP JP2006518216A patent/JP4668184B2/ja not_active Expired - Lifetime
- 2004-07-05 RU RU2006103992/04A patent/RU2352566C2/ru not_active IP Right Cessation
- 2004-07-05 BR BRPI0412447-2A patent/BRPI0412447A/pt not_active IP Right Cessation
- 2004-07-07 PE PE2004000653A patent/PE20050323A1/es not_active Application Discontinuation
- 2004-07-08 AR ARP040102412A patent/AR046494A1/es not_active Application Discontinuation
2005
- 2005-12-12 LT LT2005107A patent/LT5382B/lt not_active IP Right Cessation
- 2005-12-13 IL IL172549A patent/IL172549A0/en not_active IP Right Cessation
- 2005-12-15 IS IS8184A patent/IS2674B/is unknown
- 2005-12-23 NO NO20056175A patent/NO20056175L/no not_active Application Discontinuation
2006
- 2006-01-03 ZA ZA200600019A patent/ZA200600019B/en unknown
- 2006-01-09 EC EC2006006271A patent/ECSP066271A/es unknown
- 2006-01-10 CO CO06001617A patent/CO5640123A2/es not_active Application Discontinuation
- 2006-02-10 LV LVP-06-21A patent/LV13441B/en unknown
2008
- 2008-07-02 US US12/667,969 patent/US20100179319A1/en not_active Abandoned
2009
- 2009-08-25 CY CY20091100894T patent/CY1109327T1/el unknown

Also Published As

Publication number	Publication date
RU2352566C2 (ru)	2009-04-20
IS8184A (is)	2005-12-15
EP1656365B1 (fr)	2009-06-17
DE602004021605D1 (de)	2009-07-30
TW200510426A (en)	2005-03-16
CA2531165C (fr)	2011-08-30
NO20056175L (no)	2006-01-23
LT2005107A (en)	2006-06-27
JP2009513537A (ja)	2009-04-02
ZA200600019B (en)	2007-01-31
ATE433965T1 (de)	2009-07-15
KR20060056315A (ko)	2006-05-24
ECSP066271A (es)	2006-07-28
CY1109327T1 (el)	2014-07-02
BRPI0412447A (pt)	2006-09-19
US20100179319A1 (en)	2010-07-15
JP4668184B2 (ja)	2011-04-13
CN100558722C (zh)	2009-11-11
MXPA06000325A (es)	2006-03-30
DK1656365T3 (da)	2009-09-14
IS2674B (is)	2010-09-15
PL1656365T3 (pl)	2009-10-30
RS20050972A (sr)	2008-06-05
IL172549A0 (en)	2006-04-10
WO2005005410A1 (fr)	2005-01-20
SI1656365T1 (sl)	2009-10-31
TWI335915B (en)	2011-01-11
SG144914A1 (en)	2008-08-28
UA83666C2 (ru)	2008-08-11
ES2327123T3 (es)	2009-10-26
PE20050323A1 (es)	2005-05-16
LT5382B (lt)	2006-11-27
CA2531165A1 (fr)	2005-01-20
HRP20051019A2 (en)	2006-02-28
US8058436B2 (en)	2011-11-15
AU2004255874B2 (en)	2010-10-28
AU2004255874A1 (en)	2005-01-20
PT1656365E (pt)	2009-09-01
HK1086841A1 (en)	2006-09-29
EP1656365A1 (fr)	2006-05-17
RU2006103992A (ru)	2006-06-27
CN1820000A (zh)	2006-08-16
US20060229300A1 (en)	2006-10-12
NZ544360A (en)	2008-05-30
AR046494A1 (es)	2005-12-14
CO5640123A2 (es)	2006-05-31

Publication	Publication Date	Title
LV13441B (en)	2006-08-20	A method for the preparation of enantiomercally pure mirtazapine
US7482464B2 (en)	2009-01-27	Processes for the preparation of S-(-)-amlodipine
US20040176460A1 (en)	2004-09-09	Process for the production of 3-phenylisoserine
AU2009208107A1 (en)	2009-09-03	A process for resolving, optionally substituted, mandelic acids by salt formation with a chiral base cyclic amide
CN1356982A (zh)	2002-07-03	取代哌啶－4－酮类化合物的制备
JP2008545683A (ja)	2008-12-18	（置換された）（ｒ）−又は（ｓ）−マンデル酸の動的分割のための方法
EP2146993B1 (fr)	2015-08-05	Procédé de préparation de mirtazapine
HK1086841B (en)	2009-08-21	A method for the preparation of enantiomerically pure mirtazapine
US5578734A (en)	1996-11-26	Method for the preparation of S-(+)-ethodolic acid and saline derivatives
US20080255348A1 (en)	2008-10-16	Method for the preparation of an enantiomer of a tetracyclic benzazepine
EP0437566A1 (fr)	1991-07-24	Derives de phenyle-glycine.
WO2008026838A1 (fr)	2008-03-06	Procédé d'élaboration d'amlodipine optiquement active
US20040110957A1 (en)	2004-06-10	Process for the synthesis of an antiviral compound
KR20000070367A (ko)	2000-11-25	(1ｓ, 4ｒ)-1-아자비시클로[2,2,1]헵탄-3-온 및 (1ｒ, 4ｓ)-1-아자비시클로[2,2,1]헵탄-3-온의 제조 방법