CN1680365A - 含哌嗪环化合物的新型合成和结晶方法 - Google Patents
含哌嗪环化合物的新型合成和结晶方法 Download PDFInfo
- Publication number
- CN1680365A CN1680365A CNA2005100042908A CN200510004290A CN1680365A CN 1680365 A CN1680365 A CN 1680365A CN A2005100042908 A CNA2005100042908 A CN A2005100042908A CN 200510004290 A CN200510004290 A CN 200510004290A CN 1680365 A CN1680365 A CN 1680365A
- Authority
- CN
- China
- Prior art keywords
- methyl
- phenyl
- piperazine
- mirtazapine
- cyanopyridine
- Prior art date
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title abstract description 17
- 125000004193 piperazinyl group Chemical group 0.000 title abstract description 3
- 238000002425 crystallisation Methods 0.000 title description 5
- 230000008025 crystallization Effects 0.000 title description 4
- 230000015572 biosynthetic process Effects 0.000 title description 3
- 238000003786 synthesis reaction Methods 0.000 title description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 51
- 239000002904 solvent Substances 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 239000003513 alkali Substances 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 235000001968 nicotinic acid Nutrition 0.000 claims description 12
- 239000011664 nicotinic acid Substances 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 10
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- 239000002798 polar solvent Substances 0.000 claims 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 abstract description 70
- 229960001785 mirtazapine Drugs 0.000 abstract description 68
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 12
- 238000002360 preparation method Methods 0.000 abstract description 10
- 238000001953 recrystallisation Methods 0.000 abstract description 8
- 230000003301 hydrolyzing effect Effects 0.000 abstract 2
- FEIACFYXEWBKHU-UHFFFAOYSA-N (2-aminopyridin-3-yl)methanol Chemical compound NC1=NC=CC=C1CO FEIACFYXEWBKHU-UHFFFAOYSA-N 0.000 abstract 1
- KUSNCWLQRVMIRN-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-methyl-2-phenylethanamine Chemical compound ClCCN(C)CC(Cl)C1=CC=CC=C1 KUSNCWLQRVMIRN-UHFFFAOYSA-N 0.000 abstract 1
- PYZPABZGIRHQTA-UHFFFAOYSA-N [2-(4-methyl-2-phenylpiperazin-1-yl)pyridin-3-yl]methanol Chemical compound C1N(C)CCN(C=2C(=CC=CN=2)CO)C1C1=CC=CC=C1 PYZPABZGIRHQTA-UHFFFAOYSA-N 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 38
- 238000010992 reflux Methods 0.000 description 23
- 150000002825 nitriles Chemical class 0.000 description 21
- -1 piperazine ring compound Chemical class 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- VSAISIQCTGDGPU-UHFFFAOYSA-N phosphorus trioxide Inorganic materials O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910001950 potassium oxide Inorganic materials 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XDJWZONZDVNKDU-UHFFFAOYSA-N 1314-24-5 Chemical compound O=POP=O XDJWZONZDVNKDU-UHFFFAOYSA-N 0.000 description 2
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000024732 dysthymic disease Diseases 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000013505 freshwater Substances 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- IRMBVBDXXYXPEW-UHFFFAOYSA-N 1-methyl-3-phenylpiperazine Chemical compound C1N(C)CCNC1C1=CC=CC=C1 IRMBVBDXXYXPEW-UHFFFAOYSA-N 0.000 description 1
- DBHXNJNEECWGSO-UHFFFAOYSA-N 11h-pyrido[2,3-c][2]benzazepine Chemical class C1=NC2=NC=CC=C2CC2=CC=CC=C21 DBHXNJNEECWGSO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 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
- 150000001538 azepines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940023942 remeron Drugs 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 239000002699 waste material 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13004799P | 1999-04-19 | 1999-04-19 | |
| US60/130047 | 1999-04-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00807574A Division CN1356903A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1680365A true CN1680365A (zh) | 2005-10-12 |
Family
ID=22442814
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005100042895A Pending CN1680374A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
| CN00807574A Pending CN1356903A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
| CNA2005100042908A Pending CN1680365A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
| CNA2005100042880A Pending CN1679586A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005100042895A Pending CN1680374A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
| CN00807574A Pending CN1356903A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005100042880A Pending CN1679586A (zh) | 1999-04-19 | 2000-04-18 | 含哌嗪环化合物的新型合成和结晶方法 |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JP2004500324A (en17) |
| KR (1) | KR20020019902A (en17) |
| CN (4) | CN1680374A (en17) |
| CA (1) | CA2368815A1 (en17) |
| CZ (1) | CZ20013658A3 (en17) |
| HK (1) | HK1044116A1 (en17) |
| HR (1) | HRP20010747A2 (en17) |
| HU (1) | HUP0200839A3 (en17) |
| IL (1) | IL146023A0 (en17) |
| PL (1) | PL366289A1 (en17) |
| RU (1) | RU2001128229A (en17) |
| SK (1) | SK14672001A3 (en17) |
| TR (1) | TR200103028T2 (en17) |
| WO (1) | WO2000062782A1 (en17) |
| YU (1) | YU74101A (en17) |
| ZA (1) | ZA200108220B (en17) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6019900A (en) | 1999-11-24 | 2001-06-04 | Sumika Fine Chemicals Co., Ltd. | Anhydrous mirtazapine crystals and process for producing the same |
| AU6474200A (en) * | 1999-12-13 | 2001-06-18 | Sumika Fine Chemicals Co., Ltd. | Process for the preparation of a pyridinemethanol compound |
| US6660730B2 (en) * | 2000-11-27 | 2003-12-09 | Sumika Fine Chemicals Co., Ltd. | Anhydrous mirtazapine and process for preparing the same |
| UA83666C2 (ru) * | 2003-07-10 | 2008-08-11 | Н.В. Органон | Способ получения энантиомерно чистого миртазапина |
| ES2246161B1 (es) * | 2004-07-22 | 2007-04-01 | Medichem, S.A. | Proceso mejorado para la fabricacion de mirtazapina. |
| JP4848704B2 (ja) * | 2004-08-24 | 2011-12-28 | 住友化学株式会社 | ２−（４−メチル−２−フェニルピペラジン−１−イル）−３−シアノピリジンの製造方法 |
| 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 |
| US7994314B2 (en) | 2007-04-11 | 2011-08-09 | N.V. Organon | Method for the preparation of an enantiomerically pure benzazepine |
| MX2009010967A (es) | 2007-04-11 | 2009-12-15 | Organon Nv | Un metodo para la preparacion de mirtazapina. |
| KR101485418B1 (ko) * | 2013-05-29 | 2015-01-26 | 주식회사 메디켐코리아 | 고순도 미르타자핀의 제조방법 |
| JP6571497B2 (ja) * | 2015-11-13 | 2019-09-04 | 株式会社トクヤマ | ミルタザピンの製造方法 |
| JP2017088564A (ja) * | 2015-11-13 | 2017-05-25 | 株式会社トクヤマ | ミルタザピンの製造方法 |
| CN108191873B (zh) * | 2018-01-08 | 2021-09-24 | 山东省食品药品检验研究院 | 一种盐酸米安色林的纯化方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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. |
-
2000
- 2000-04-18 PL PL00366289A patent/PL366289A1/xx unknown
- 2000-04-18 WO PCT/US2000/010357 patent/WO2000062782A1/en not_active Application Discontinuation
- 2000-04-18 CA CA002368815A patent/CA2368815A1/en not_active Abandoned
- 2000-04-18 SK SK1467-2001A patent/SK14672001A3/sk unknown
- 2000-04-18 HR HR20010747A patent/HRP20010747A2/hr not_active Application Discontinuation
- 2000-04-18 JP JP2000611918A patent/JP2004500324A/ja not_active Withdrawn
- 2000-04-18 IL IL14602300A patent/IL146023A0/xx unknown
- 2000-04-18 RU RU2001128229/04A patent/RU2001128229A/ru not_active Application Discontinuation
- 2000-04-18 HK HK02105027.4A patent/HK1044116A1/zh unknown
- 2000-04-18 CN CNA2005100042895A patent/CN1680374A/zh active Pending
- 2000-04-18 YU YU74101A patent/YU74101A/sh unknown
- 2000-04-18 CN CN00807574A patent/CN1356903A/zh active Pending
- 2000-04-18 CZ CZ20013658A patent/CZ20013658A3/cs unknown
- 2000-04-18 CN CNA2005100042908A patent/CN1680365A/zh active Pending
- 2000-04-18 KR KR1020017013267A patent/KR20020019902A/ko not_active Abandoned
- 2000-04-18 CN CNA2005100042880A patent/CN1679586A/zh active Pending
- 2000-04-18 HU HU0200839A patent/HUP0200839A3/hu unknown
- 2000-04-18 TR TR2001/03028T patent/TR200103028T2/xx unknown
-
2001
- 2001-10-05 ZA ZA200108220A patent/ZA200108220B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL146023A0 (en) | 2002-07-25 |
| CN1680374A (zh) | 2005-10-12 |
| HUP0200839A2 (en) | 2002-08-28 |
| HK1044116A1 (zh) | 2002-10-11 |
| HUP0200839A3 (en) | 2003-05-28 |
| WO2000062782A1 (en) | 2000-10-26 |
| CZ20013658A3 (cs) | 2002-08-14 |
| CN1356903A (zh) | 2002-07-03 |
| PL366289A1 (en) | 2005-01-24 |
| KR20020019902A (ko) | 2002-03-13 |
| TR200103028T2 (tr) | 2002-01-21 |
| ZA200108220B (en) | 2006-02-26 |
| YU74101A (sh) | 2004-09-03 |
| RU2001128229A (ru) | 2003-07-10 |
| SK14672001A3 (sk) | 2002-11-06 |
| JP2004500324A (ja) | 2004-01-08 |
| CN1679586A (zh) | 2005-10-12 |
| HRP20010747A2 (en) | 2002-12-31 |
| CA2368815A1 (en) | 2000-10-26 |
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