DK160305B - Norscopin og fremgangsmaade til fremstilling heraf samt dets anvendelse som mellemprodukt - Google Patents
Norscopin og fremgangsmaade til fremstilling heraf samt dets anvendelse som mellemprodukt Download PDFInfo
- Publication number
- DK160305B DK160305B DK182083A DK182083A DK160305B DK 160305 B DK160305 B DK 160305B DK 182083 A DK182083 A DK 182083A DK 182083 A DK182083 A DK 182083A DK 160305 B DK160305 B DK 160305B
- Authority
- DK
- Denmark
- Prior art keywords
- norscopin
- salts
- preparation
- general formula
- procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- 239000013067 intermediate product Substances 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000004678 hydrides Chemical class 0.000 claims abstract 3
- 238000003776 cleavage reaction Methods 0.000 claims abstract 2
- 230000007017 scission Effects 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims 1
- MOYZEMOPQDTDHA-YQYZCKNZSA-N norhyoscine Chemical compound C1([C@H](C(=O)OC2C[C@@H]3N[C@@H]([C@H]4O[C@H]43)C2)CO)=CC=CC=C1 MOYZEMOPQDTDHA-YQYZCKNZSA-N 0.000 abstract description 4
- MOYZEMOPQDTDHA-UHFFFAOYSA-N norscopolamine Natural products C1C(C2OC22)NC2CC1OC(=O)C(CO)C1=CC=CC=C1 MOYZEMOPQDTDHA-UHFFFAOYSA-N 0.000 abstract description 3
- 238000005984 hydrogenation reaction Methods 0.000 abstract 1
- 239000012442 inert solvent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001813 broncholytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- PMDQSBZXEATWCG-DEKXFLRUSA-N gxs4t1a55n Chemical compound Cl.C1([C@H](C(=O)OC2C[C@@H]3N[C@@H]([C@H]4O[C@H]43)C2)CO)=CC=CC=C1 PMDQSBZXEATWCG-DEKXFLRUSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- -1 suitable Natural products 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Steroid Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Financial Or Insurance-Related Operations Such As Payment And Settlement (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Control Of Motors That Do Not Use Commutators (AREA)
- Liquid Deposition Of Substances Of Which Semiconductor Devices Are Composed (AREA)
- Physical Deposition Of Substances That Are Components Of Semiconductor Devices (AREA)
- Forklifts And Lifting Vehicles (AREA)
Description
i
DK 160305 B
Opfindelsen angår den hidtil ukendte forbindelse norscopin med formlen
N - H
HO
dens syreadditionssalte samt en fremgangsmåde til dens 15 fremstilling.
Norscopin er et værdifuldt forprodukt, f.eks. til fremstilling af hidtil ukendte 6,11-dihydro-diben-zo-[b,e]-thiepin-ll-N-alkyl-norscopinethere med den almen formel II
20 Γ ©
CH, R N
A
J \ / s>=< K / X©
f X
30 X-/ 'h 35 hvori R betegner en ligekædet eller forgrenet alkylgrup-pe med 1 til 10 carbonatomer, og betegner en farmakologisk acceptabel anion, som f.eks. et halogenatom eller resten af en organisk sulfonsyre. Disse stoffer
DK 160305 B
2 er på deres side værdifulde farmaceutika med et godt afstemt forhold mellem anticholinerg og antihistami-nisk virkning. De egner sig derfor fremragende til anvendelse som broncholytika. Disse stoffer er beskrevet 5 i tysk patentansøgning P 32 11 185.1 (dansk ansøgning nr. 0947/83).
Omdannelsen af norscopin til norscopin-etherne med den ovenfor anførte almene formel II kan foregå på den måde, at man først (f.eks. ved sædvanlig 10 N-alkylering med alkylhalogenider) fremstiller N-alkyl-norscopinerne med den almene formel III
N - R
15 / in 20 ΗθΝϊ
hvori R har den ovennævnte betydning, og derefter omsætter disse med forbindelser med den almene formel IV
25 I IV
X H
30 hvori X betegner en let fraspaltelig gruppe (f.eks. et halogenatom), til tertiære forbindelser med den almene formel V
DK 160305B
3
R
N" '
hvori R har den ovennævnte betydning, og dernæst overfører sidstnævnte med sædvanlige kvaterniseringsmidler 15 med den almene formel VI
ch3 - X VI
hvori X har de ovennævnte betydninger, i de kvaternære salte med den almene formel II. Med hensyn til nærmere 20 enkeltheder ved syntesen af forbindelser med den almene formel II henvises der til den allerede nævnte tyske patentansøgning P 32 11 185.1.
Fremgangsmåden ifølge opfindelsen til fremstilling af norscopin er ejendommelig ved, at man behandler 25 norscopolamin eller dettes salte med egnede komplekse metalhydrider (fortrinsvis ved stuetemperatur eller lavere temperaturer) i et opløsningsmiddel. Særlig egnet er metalborhydrider og herunder igen natriumborhydrid (NaBH^). Også lithiumalanat er principielt egnet, men 30 herved skal der dog til undgåelse af sidereaktioner anvendes temperaturer på 0°C og mindre.
Som opløsningsmiddel til den ovennævnte omsætning kommer fremfor alt ethanol i betragtning. Højere alkoholer og andre organiske opløsningsmidler (f.eks.
35 ethere) er mindre gunstige, da de fortrinsvis som udgangsprodukter anvendte norscopolaminsalte er tungt-opløselige deri. Heller ikke methanol er særlig velegnet, da det f.eks. meget hurtigt sønderdeler natriumborhydrid allerede ved 0°C, således at den anvendte DK 160305 B j i 4 | mængde af dette reagens forøges i unødig grad. Hydro- genolysen kan også foregå i vand, når f.eks. pH-værdien indstillet på ca. 6 til 7. Den påfølgende isolering af norscopin fra vand er dog mere besværlig end fra 5 ethanol.
Fremstillingen af det som udgangsprodukt benyttede norscopolamin fremgår af de tyske fremlæggelsesskrifter nr. 1 670 257 og 1 670 258.
Opfindelsen belyses nærmere ved hjælp af det 10 efterfølgende eksempel.
Eksempel
Norscopin og norscopin-hydrochlorid.
32,6 g (0,1 mol) norscopolamin-hydrochlorid sus- I
penderes i 350 ml ethanol og tilsættes ved en tempera-15 tur på 20°C og under vedvarende omrøring 3,78 g (0,1 mol) natriumborhydrid i seks portioner hver med 20 minutters mellemrum. Man lader blandingen efterreagere i 12 timer. Hydrogenolysen er afsluttet efter dette tidsrum. Ved -5 til -10°C tilledes der nu under en nitrogenatmosfære 20 hydrogenchloridgas til sur reaktion, og opløsningen vaskes fri for hydrogenchlorid med 1,5 liter ether.
De efter tørring fint revne krystaller suspenderer man i 2 liter methylenchlorid, opvarmer til kogning og til- . leder ammoniak til det kogende methylenchlorid indtil 25 fuldstændig omsætning til dannelse af basen. Efter fra-skillelse af de organiske salte afdestilleres methylen-chloridet ved 30°C under formindsket tryk.
Norscopinet krystalliserer i farveløse krystaller.
30 Smeltepunkt 198-202°C (sønderdeling).
Udbytte: 12,0 g (85,7% af det teoretiske).
Hydrochloridet kan fremstilles ved sædvanlige metoder. Farveløse krystaller (ethanol), smeltepunkt 292-293°C (sønderdeling),(omdannelsespunkt ^205°C) .
35 Ved hjælp af elementæranalyse og spektre be kræftes det, at der foreligger denne forbindelse.
Claims (5)
1. Norscopin med formlen I N - H 10 \ N HO og dettes syreadditionssalte.
2. Fremgangsmåde til fremstilling af norscopin og dettes salte, kendetegnet ved, at man underkaster norscopolamin eller dets salte hydrogeno-lytisk spaltning med et komplekst hydrid i et egnet opløsningsmiddel.
3. Fremgangsmåde ifølge krav 2, kendeteg net ved, at man som komplekst hydrid anvender et metalborhydrid.
4. Fremgangsmåde ifølge krav 3, kendetegnet ved, at man arbejder med natriumborhydrid i etha- 25 nol ved stuetemperatur.
5. Anvendelse af norscopin til fremstilling af farmaceutisk aktive stoffer med den almene formel II DK 160305 B © ra3. /R N °^A> §h ^ tt \S II *· — 15 hvori R betegner en ligekædet eller forgrenet alkylgrup-pe med 1 til 10 carbonatomer, og betegner en farmakologisk acceptabel anion, som f.eks. et halogenatom eller resten af en organisk sulfonsyre.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823215490 DE3215490A1 (de) | 1982-04-26 | 1982-04-26 | Neues vorprodukt, verfahren zu seiner herstellung und seine verwendung |
| DE3215490 | 1982-04-26 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK182083D0 DK182083D0 (da) | 1983-04-25 |
| DK182083A DK182083A (da) | 1983-10-27 |
| DK160305B true DK160305B (da) | 1991-02-25 |
| DK160305C DK160305C (da) | 1991-07-29 |
Family
ID=6161960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK182083A DK160305C (da) | 1982-04-26 | 1983-04-25 | Norscopin og fremgangsmaade til fremstilling heraf samt dets anvendelse som mellemprodukt |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4755603A (da) |
| EP (1) | EP0093343B1 (da) |
| JP (1) | JPS58201778A (da) |
| KR (1) | KR900004128B1 (da) |
| AT (1) | ATE18401T1 (da) |
| AU (1) | AU557702B2 (da) |
| CA (1) | CA1254565A (da) |
| CS (1) | CS236793B2 (da) |
| DD (1) | DD209631A5 (da) |
| DE (2) | DE3215490A1 (da) |
| DK (1) | DK160305C (da) |
| ES (1) | ES521808A0 (da) |
| FI (1) | FI72976C (da) |
| GR (1) | GR78838B (da) |
| HU (1) | HU193162B (da) |
| IE (1) | IE55356B1 (da) |
| IL (1) | IL68478A0 (da) |
| NO (1) | NO157451C (da) |
| NZ (1) | NZ203979A (da) |
| PL (1) | PL138641B1 (da) |
| PT (1) | PT76583B (da) |
| YU (1) | YU43827B (da) |
| ZA (1) | ZA832882B (da) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3211185A1 (de) * | 1982-03-26 | 1983-09-29 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue quartaere 6,11-dihydro-dibenzo-(b,e)-thiepin-11-n-alkyl- norscopinether und verfahren zu deren herstellung |
-
1982
- 1982-04-26 DE DE19823215490 patent/DE3215490A1/de not_active Withdrawn
-
1983
- 1983-04-13 FI FI831233A patent/FI72976C/fi not_active IP Right Cessation
- 1983-04-20 DD DD83250032A patent/DD209631A5/de not_active IP Right Cessation
- 1983-04-21 GR GR71158A patent/GR78838B/el unknown
- 1983-04-21 PT PT76583A patent/PT76583B/pt not_active IP Right Cessation
- 1983-04-22 NZ NZ203979A patent/NZ203979A/en unknown
- 1983-04-22 AT AT83103936T patent/ATE18401T1/de not_active IP Right Cessation
- 1983-04-22 EP EP83103936A patent/EP0093343B1/de not_active Expired
- 1983-04-22 DE DE8383103936T patent/DE3362384D1/de not_active Expired
- 1983-04-25 HU HU831416A patent/HU193162B/hu not_active IP Right Cessation
- 1983-04-25 CA CA000426596A patent/CA1254565A/en not_active Expired
- 1983-04-25 PL PL1983241634A patent/PL138641B1/pl unknown
- 1983-04-25 ZA ZA832882A patent/ZA832882B/xx unknown
- 1983-04-25 ES ES521808A patent/ES521808A0/es active Granted
- 1983-04-25 NO NO831446A patent/NO157451C/no unknown
- 1983-04-25 JP JP58072765A patent/JPS58201778A/ja active Granted
- 1983-04-25 CS CS832918A patent/CS236793B2/cs unknown
- 1983-04-25 IE IE937/83A patent/IE55356B1/en not_active IP Right Cessation
- 1983-04-25 IL IL68478A patent/IL68478A0/xx not_active IP Right Cessation
- 1983-04-25 YU YU937/83A patent/YU43827B/xx unknown
- 1983-04-25 DK DK182083A patent/DK160305C/da not_active IP Right Cessation
- 1983-04-25 KR KR1019830001743A patent/KR900004128B1/ko not_active Expired
- 1983-04-26 AU AU13946/83A patent/AU557702B2/en not_active Ceased
-
1987
- 1987-05-26 US US07/053,956 patent/US4755603A/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK159777B (da) | N-alkyl-norscopiner og fremgangsmaade til fremstilling heraf samt deres anvendelse som mellemprodukter | |
| EP0125783B1 (en) | Dopamine-beta-hydroxylase inhibitors | |
| CA2334821C (en) | Chemical synthesis of morpholine derivatives | |
| JPS6039678B2 (ja) | 新規インド−ル誘導体の製法 | |
| IE42978B1 (en) | Triaryl alkyl azabicyclo compounds | |
| EP0052333B1 (en) | 4-fluoro-5-oxypyrazole derivate and preparation thereof | |
| DK160305B (da) | Norscopin og fremgangsmaade til fremstilling heraf samt dets anvendelse som mellemprodukt | |
| US4251521A (en) | Alkyl diaryl sulfonium salts | |
| JPS60202859A (ja) | ３―アミノアゼチジン化合物及びその製造方法 | |
| NO139479B (no) | Fremgangsmaate for fremstilling av 4-amino-3,5-dihalogen-fenyl-etanolaminer | |
| CA2005547C (en) | Derivatives of 1,7' (imidazo-(1,2-a)-pyridine)5'-(6'h)ones | |
| EP0062068B1 (en) | N-phthalidyl-5-fluorouracil derivatives | |
| JPS59206339A (ja) | 第２級アミンの製法 | |
| EP0364091A1 (en) | Antipsychotic 4-(4-(3-benzisothiazolyl)-1-piperazinyl)butyl bridged bicyclic imides | |
| US2797222A (en) | Preparation of neopine | |
| NO142909B (no) | Analogifremgangsmaate ved fremstilling av terapeutisk aktive 4-benzazoninderivater. | |
| KR100458170B1 (ko) | 2-[3-메톡시-4-(2,2,2-트리플로로에톡시)2-피리딜]메틸설피닐-1h-벤즈이미다졸의신규제조방법 | |
| JPS5936633B2 (ja) | ベンゾクマリン誘導体の製造法 | |
| KR20040049044A (ko) | 1,2,3-트리스(2-디에틸아미노에톡시)벤젠의 제조방법 | |
| RU2292340C1 (ru) | Способ получения r-метилпроизводных 3,5-диамино-1,2,4-триазола | |
| CS209608B1 (cs) | D-1-hydroxyethy1-8-methoxykarbony 1-6-methylergolin-I | |
| NO126575B (da) | ||
| GB2059953A (en) | 3-Aryl-3-aryloxyalkylamines | |
| JPS603063B2 (ja) | インダゾ−ル誘導体の製法 | |
| JPH01199968A (ja) | ４−シアノキヌクリジンの製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |