LT5382B - ENANTIOMERISKAI GRYNO MIRTAZAPINO GAVIMO BuDAS - Google Patents

ENANTIOMERISKAI GRYNO MIRTAZAPINO GAVIMO BuDAS Download PDF

Info

Publication number: LT5382B
Authority: LT; Lithuania
Prior art keywords: acid; mirtazapine; combination; compound; solvent
Prior art date: 2003-07-10

Application number

LT2005107A

Other languages

English (en)

Lithuanian (lt)

Other versions

LT2005107A (en

Inventor

Johannes Hubertus Wieringa

Adrianus Antonius Martinus Van De Ven

Gerardus Johannes Kemperman

Original Assignee

Akzo Nobel N. V.

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

2005-12-12

Publication date

2006-11-27

2005-12-12 Application filed by Akzo Nobel N. V. filed Critical Akzo Nobel N. V.

2006-06-27 Publication of LT2005107A publication Critical patent/LT2005107A/xx

2006-11-27 Publication of LT5382B publication Critical patent/LT5382B/lt

Links

RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 title claims abstract description 37
229960001785 mirtazapine Drugs 0.000 title claims abstract description 37
238000000034 method Methods 0.000 title claims abstract description 34
238000002360 preparation method Methods 0.000 title claims abstract description 13
239000002253 acid Substances 0.000 claims abstract description 52
150000001875 compounds Chemical class 0.000 claims abstract description 36
239000002904 solvent Substances 0.000 claims abstract description 23
238000006798 ring closing metathesis reaction Methods 0.000 claims abstract description 20
239000003960 organic solvent Substances 0.000 claims abstract description 11
229920000137 polyphosphoric acid Polymers 0.000 claims description 21
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 18
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 14
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 claims description 10
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 10
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 9
KKADPXVIOXHVKN-UHFFFAOYSA-N 4-hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=C(O)C=C1 KKADPXVIOXHVKN-UHFFFAOYSA-N 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims 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 claims description 3
150000007522 mineralic acids Chemical group 0.000 claims description 2
238000007363 ring formation reaction Methods 0.000 claims description 2
230000000707 stereoselective effect Effects 0.000 claims description 2
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 24
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
239000000243 solution Substances 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
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
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
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 9
239000010410 layer Substances 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
239000002585 base Substances 0.000 description 7
RONZAEMNMFQXRA-MRXNPFEDSA-N esmirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)C[C@@H]2C2=CC=CC=C21 RONZAEMNMFQXRA-MRXNPFEDSA-N 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
150000003839 salts Chemical class 0.000 description 6
239000007858 starting material Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
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 4
-1 Conor and Leonard Chemical class 0.000 description 4
239000005909 Kieselgur Substances 0.000 description 4
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
230000015572 biosynthetic process Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
239000012453 solvate Substances 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
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
239000003153 chemical reaction reagent Substances 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
PVNBEADBJHJCRN-PKLMIRHRSA-N [2-[(2s)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl]methanol;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@@H]2N(CCN(C2)C)C=2C(=CC=CN=2)CO)=CC=CC=C1 PVNBEADBJHJCRN-PKLMIRHRSA-N 0.000 description 2
150000008065 acid anhydrides Chemical class 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
238000004587 chromatography analysis Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
238000010438 heat treatment Methods 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
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-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
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
PVNBEADBJHJCRN-NTISSMGPSA-N C(C(=O)O)(=O)O.OCC=1C(=NC=CC1)N1[C@@H](CN(CC1)C)C1=CC=CC=C1 Chemical compound C(C(=O)O)(=O)O.OCC=1C(=NC=CC1)N1[C@@H](CN(CC1)C)C1=CC=CC=C1 PVNBEADBJHJCRN-NTISSMGPSA-N 0.000 description 1
208000020401 Depressive disease Diseases 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
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-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
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
238000003556 assay Methods 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 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
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-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
238000004321 preservation Methods 0.000 description 1
238000011002 quantification Methods 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000004366 reverse phase liquid chromatography 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
238000010971 suitability test Methods 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)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

LT2005107A 2003-07-10 2005-12-12 ENANTIOMERISKAI GRYNO MIRTAZAPINO GAVIMO BuDAS LT5382B (lt)

Applications Claiming Priority (1)

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

Publications (2)

Publication Number	Publication Date
LT2005107A LT2005107A (en)	2006-06-27
LT5382B true LT5382B (lt)	2006-11-27

Family

ID=34042934

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LT2005107A LT5382B (lt)	2003-07-10	2005-12-12	ENANTIOMERISKAI GRYNO MIRTAZAPINO GAVIMO BuDAS

Country Status (35)

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

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
CN102126982A (zh) *	2005-09-26	2011-07-20	住友化学株式会社	光学活性的哌嗪化合物的制造方法
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
EP2119709A4 (en) *	2007-02-09	2011-08-17	Kaneka Corp	PROCESS FOR PREPARING OPTICALLY ACTIVE 2-ARYLPIPERAZINE DERIVATIVE
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
MX2009010967A (es) *	2007-04-11	2009-12-15	Organon Nv	Un metodo para la preparacion de mirtazapina.
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
US10603272B2 (en)	2015-02-27	2020-03-31	Kindred Biosciences, Inc.	Stimulation of appetite and treatment of anorexia in dogs and cats
KR102540021B1 (ko) *	2020-12-02	2023-06-07	(주)유케이케미팜	대량 생산에 적합한 미르타자핀의 제조방법

Citations (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4062848A (en)	1975-04-05	1977-12-13	Akzona Incorporated	Tetracyclic compounds
WO1999025356A1 (en)	1997-11-14	1999-05-27	Akzo Nobel N.V.	Use of mirtazapine for treating sleep apneas
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Also Published As

Publication number	Publication date
SI1656365T1 (sl)	2009-10-31
TW200510426A (en)	2005-03-16
PT1656365E (pt)	2009-09-01
CN100558722C (zh)	2009-11-11
MXPA06000325A (es)	2006-03-30
BRPI0412447A (pt)	2006-09-19
IL172549A0 (en)	2006-04-10
RU2006103992A (ru)	2006-06-27
IS8184A (is)	2005-12-15
TWI335915B (en)	2011-01-11
PE20050323A1 (es)	2005-05-16
UA83666C2 (ru)	2008-08-11
EP1656365A1 (en)	2006-05-17
RU2352566C2 (ru)	2009-04-20
PL1656365T3 (pl)	2009-10-30
RS20050972A (sr)	2008-06-05
LT2005107A (en)	2006-06-27
CN1820000A (zh)	2006-08-16
CY1109327T1 (el)	2014-07-02
AU2004255874A1 (en)	2005-01-20
HRP20051019A2 (en)	2006-02-28
KR20060056315A (ko)	2006-05-24
SG144914A1 (en)	2008-08-28
CA2531165A1 (en)	2005-01-20
AR046494A1 (es)	2005-12-14
JP2009513537A (ja)	2009-04-02
HK1086841A1 (en)	2006-09-29
NO20056175L (no)	2006-01-23
US20060229300A1 (en)	2006-10-12
US20100179319A1 (en)	2010-07-15
LV13441B (en)	2006-08-20
US8058436B2 (en)	2011-11-15
NZ544360A (en)	2008-05-30
CO5640123A2 (es)	2006-05-31
ECSP066271A (es)	2006-07-28
DE602004021605D1 (de)	2009-07-30
AU2004255874B2 (en)	2010-10-28
JP4668184B2 (ja)	2011-04-13
WO2005005410A1 (en)	2005-01-20
ES2327123T3 (es)	2009-10-26
IS2674B (is)	2010-09-15
ZA200600019B (en)	2007-01-31
ATE433965T1 (de)	2009-07-15
CA2531165C (en)	2011-08-30
EP1656365B1 (en)	2009-06-17
DK1656365T3 (da)	2009-09-14

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