NZ546768A - Resolution of a narwedine amide derivative and the synthesis of galantamine - Google Patents
Resolution of a narwedine amide derivative and the synthesis of galantamineInfo
- Publication number
- NZ546768A NZ546768A NZ546768A NZ54676804A NZ546768A NZ 546768 A NZ546768 A NZ 546768A NZ 546768 A NZ546768 A NZ 546768A NZ 54676804 A NZ54676804 A NZ 54676804A NZ 546768 A NZ546768 A NZ 546768A
- Authority
- NZ
- New Zealand
- Prior art keywords
- bromoamide
- mixed solution
- galantamine
- racemic
- amine
- Prior art date
Links
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 title claims abstract description 24
- 229960003980 galantamine Drugs 0.000 title claims abstract description 18
- -1 narwedine amide Chemical class 0.000 title claims abstract description 11
- QENVUHCAYXAROT-UHFFFAOYSA-N Galanthaminon Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(=O)C=C2 QENVUHCAYXAROT-UHFFFAOYSA-N 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 9
- 238000003786 synthesis reaction Methods 0.000 title abstract description 9
- WCRYNEMFWLZAAZ-WMLDXEAASA-N Narwedine Natural products COc1ccc2CCCC[C@@]34C=CC(=O)C[C@@H]3Oc1c24 WCRYNEMFWLZAAZ-WMLDXEAASA-N 0.000 title abstract description 7
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 title abstract description 5
- FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 23
- 150000001412 amines Chemical class 0.000 claims abstract description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000013078 crystal Substances 0.000 claims abstract description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims abstract description 8
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 230000003287 optical effect Effects 0.000 claims abstract description 8
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 claims abstract description 4
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 4
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000010899 nucleation Methods 0.000 claims abstract description 4
- 239000011259 mixed solution Substances 0.000 claims abstract 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract 6
- 239000000243 solution Substances 0.000 claims abstract 5
- 239000011149 active material Substances 0.000 claims abstract 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 5
- 229940086542 triethylamine Drugs 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- ASUTZQLVASHGKV-SUYBPPKGSA-N ent-galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@@]23[C@H]1C[C@H](O)C=C2 ASUTZQLVASHGKV-SUYBPPKGSA-N 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- BCDGQXUMWHRQCB-UHFFFAOYSA-N glycine methyl ketone Natural products CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 claims 1
- 125000005270 trialkylamine group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 description 7
- QENVUHCAYXAROT-YOEHRIQHSA-N Narwedine Chemical class O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1CC(=O)C=C2 QENVUHCAYXAROT-YOEHRIQHSA-N 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- QENVUHCAYXAROT-RHSMWYFYSA-N (+)-narwedine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@@]23[C@H]1CC(=O)C=C2 QENVUHCAYXAROT-RHSMWYFYSA-N 0.000 description 1
- 229940124810 Alzheimer's drug Drugs 0.000 description 1
- 241000234270 Amaryllidaceae Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 235000015256 Chionanthus virginicus Nutrition 0.000 description 1
- 241000234271 Galanthus Species 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 238000000605 extraction Methods 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
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/06—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50646903P | 2003-09-26 | 2003-09-26 | |
| PCT/US2004/031936 WO2005030713A2 (en) | 2003-09-26 | 2004-09-27 | Resolution of a narwedine amide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ546768A true NZ546768A (en) | 2009-07-31 |
Family
ID=34393160
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ546768A NZ546768A (en) | 2003-09-26 | 2004-09-27 | Resolution of a narwedine amide derivative and the synthesis of galantamine |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7307162B2 (enExample) |
| EP (1) | EP1670767B2 (enExample) |
| JP (1) | JP5020633B2 (enExample) |
| CN (1) | CN1875004B (enExample) |
| AU (1) | AU2004276354B2 (enExample) |
| CA (1) | CA2540248C (enExample) |
| IL (1) | IL174551A0 (enExample) |
| NZ (1) | NZ546768A (enExample) |
| WO (1) | WO2005030713A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090253654A1 (en) | 2005-09-22 | 2009-10-08 | Galantos Pharma Gmbh | Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment |
| US7985879B2 (en) * | 2007-04-12 | 2011-07-26 | Scinopharm Taiwan Ltd. | Process for making galantamine |
| ES2463715T3 (es) | 2008-04-14 | 2014-05-29 | Neurodyn Life Sciences Inc. | Derivados de galantamina como profármacos para el tratamiento de enfermedades del cerebro humano |
| WO2011151359A1 (en) | 2010-06-02 | 2011-12-08 | Noscira, S.A. | Combined treatment with a cholinesterase inhibitor and a thiadiazolidinedione derivative |
| BG66818B1 (bg) | 2013-03-07 | 2019-01-31 | Berbee Beheer B. V. | Състав на екстракт от hippeastrum papilio за производство на лекарствени средства и хранителни добавки |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG28325A1 (en) * | 1978-11-21 | 1980-04-15 | Vlakhov | Method of obtaining of enons navedine type and their derivatives |
| US4290862A (en) * | 1979-11-14 | 1981-09-22 | Edinen Centar P Chimia | Method for the preparation of narwedine-type enones |
| US5428159A (en) | 1994-04-08 | 1995-06-27 | Ciba-Geigy Corporation | Method of manufacture of (-)-galanthamine in high yield and purity substantially free of epigalanthamine |
| US6407229B1 (en) * | 1994-10-21 | 2002-06-18 | Sanochemia Pharmazeutika Ag | Processes for the preparation of derivatives of 4a,5,9,10,11,12-hexahydro-6H-benzofuro-[3a,3,2-ef][2] benzazapine |
| GB9506843D0 (en) * | 1995-04-03 | 1995-05-24 | Chiroscience Ltd | Oxidative process and products thereof |
| US6018043A (en) * | 1995-04-06 | 2000-01-25 | Janssen Pharmaceutica, N.V. | Process for preparing galanthamine derivatives by asymmetric reduction |
| GB9707413D0 (en) * | 1997-04-11 | 1997-05-28 | Chiroscience Ltd | Process |
-
2004
- 2004-09-27 AU AU2004276354A patent/AU2004276354B2/en not_active Ceased
- 2004-09-27 JP JP2006528320A patent/JP5020633B2/ja not_active Expired - Fee Related
- 2004-09-27 CN CN2004800276266A patent/CN1875004B/zh not_active Expired - Fee Related
- 2004-09-27 WO PCT/US2004/031936 patent/WO2005030713A2/en not_active Ceased
- 2004-09-27 CA CA2540248A patent/CA2540248C/en not_active Expired - Fee Related
- 2004-09-27 US US10/951,748 patent/US7307162B2/en not_active Expired - Lifetime
- 2004-09-27 EP EP04789228.6A patent/EP1670767B2/en not_active Expired - Lifetime
- 2004-09-27 NZ NZ546768A patent/NZ546768A/en not_active IP Right Cessation
-
2006
- 2006-03-26 IL IL174551A patent/IL174551A0/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP1670767A4 (en) | 2007-08-29 |
| CN1875004A (zh) | 2006-12-06 |
| WO2005030713A3 (en) | 2006-01-26 |
| WO2005030713A2 (en) | 2005-04-07 |
| US20050070522A1 (en) | 2005-03-31 |
| CA2540248A1 (en) | 2005-04-07 |
| EP1670767B2 (en) | 2014-10-29 |
| EP1670767A2 (en) | 2006-06-21 |
| JP5020633B2 (ja) | 2012-09-05 |
| AU2004276354B2 (en) | 2009-07-09 |
| AU2004276354A1 (en) | 2005-04-07 |
| CN1875004B (zh) | 2010-06-23 |
| US7307162B2 (en) | 2007-12-11 |
| EP1670767B1 (en) | 2011-08-24 |
| IL174551A0 (en) | 2006-08-20 |
| JP2007506794A (ja) | 2007-03-22 |
| CA2540248C (en) | 2010-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1546149B1 (en) | Modified pictet-spengler reaction and products prepared therefrom | |
| WO2007119114A2 (en) | Improved synthesis and preparations of duloxetine salts | |
| EP1670767B1 (en) | Resolution of a narwedine amide derivative | |
| JP5406194B2 (ja) | Ｒ−ゴシポールｌ−フェニルアラニノールジエナミンを調製するための方法 | |
| AU2009264395B2 (en) | Process for the preparation of clopidogrel hydrogen sulfate crystalline form I | |
| JP4056565B2 (ja) | 炭素環式立体異性体混合物の分割方法 | |
| KR100933172B1 (ko) | 아토르바스타틴 칼슘염의 개선된 제조방법 | |
| KR100523125B1 (ko) | 단일 에난티오머 나웨딘을 제조하기 위한 방법 | |
| CN119841759B (zh) | 一种沙库必曲中间体的制备方法 | |
| WO2010068049A2 (en) | Process for preparing (r)-(+)-lansoprazole and intermediate used therein | |
| FR2555580A1 (fr) | Nouveaux composes azabicycliques, procede pour les preparer et medicaments les contenant | |
| EP1484315A1 (en) | Process for production of optically active beta-phenylalanine | |
| KR100397491B1 (ko) | 광학활성 (ｓ)-벤즈옥사진 유도체 및 그의 제조방법 | |
| KR20060125218A (ko) | 광학활성 벤족사진 유도체의 제조방법 | |
| WO1999058493A2 (en) | Process for the preparation of optically pure phenylalanine | |
| HU206696B (en) | Process for producing enanthiomeres of raceme trans-/+/-2,3-epoxy-3-?4-methoxy-phenyl/-propionic acid methyl-ester | |
| WO2009050735A1 (en) | A novel polymorph of levetiracetam and a process for its preparation | |
| JP2004503539A (ja) | 望ましくない鏡像体のｉｎｓｉｔｕ同時ラセミ化を伴うピペリドン誘導体の鏡像体の分離 | |
| HK1019608A (en) | Preparation of (7s,trans)-2-(2-pyrimidinyl)-7-(hydroxymethyl)octahydro-2h-pyrido[1,2-a]pyrazine | |
| KR20050000463A (ko) | 광학활성 벤족사진 유도체의 제조방법 | |
| MXPA99009247A (en) | Process for preparing single enantiomer narwedine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ASS | Change of ownership |
Owner name: SCINOPHARM TAIWAN, CN Free format text: OLD OWNER(S): TSUNG-YU HSIAO; GEORGE SCHLOEMER |
|
| S883 | Correction of error according to section 88(3) (mistake in register caused on part of patentee or applicant) |
Free format text: THE ORIGINAL APPLICATION SHOULD HAVE BEEN FILED IN THE NAME OF THE INVENTORS, WHO SUBSEQUENTLY ASSIGNED THEIR RIGHTS TO THE APPLICATION TO THE APPLICANT |
|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |