NO872810L - Fremgangsmaate for fremstilling av en terapeutisk aktiv forbindelse. - Google Patents
Fremgangsmaate for fremstilling av en terapeutisk aktiv forbindelse.Info
- Publication number
- NO872810L NO872810L NO872810A NO872810A NO872810L NO 872810 L NO872810 L NO 872810L NO 872810 A NO872810 A NO 872810A NO 872810 A NO872810 A NO 872810A NO 872810 L NO872810 L NO 872810L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- preparing
- procedure
- minoxidil
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 15
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 9
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 229960003632 minoxidil Drugs 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- USSBDBZGEDUBHE-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate Chemical compound [Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O USSBDBZGEDUBHE-UHFFFAOYSA-L 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IDCARVYLHZLEMC-UHFFFAOYSA-N (2,6-diaminopyrimidin-4-yl) 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC(N)=NC(N)=N1 IDCARVYLHZLEMC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- SWELIMKTDYHAOY-UHFFFAOYSA-N 2,4-diamino-6-hydroxypyrimidine Chemical compound NC1=CC(=O)N=C(N)N1 SWELIMKTDYHAOY-UHFFFAOYSA-N 0.000 description 1
- SXIUYERFFIKRTI-UHFFFAOYSA-N C1=CC(C)=CC=C1S(=O)(=O)OC1=CC(N)=[N+]([O-])C(N)=N1 Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC(N)=[N+]([O-])C(N)=N1 SXIUYERFFIKRTI-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004687 hexahydrates Chemical class 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/50—Three nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Denne oppfinnelse angår en fremgangsmåte for fremstilling av 2,4-diamino-3-oksy-6-piperidylpyrimidin eller Minoxidil. Minoxidil som har formelen
er anvendelig som antihypertensivt middel.
Fremgangsmåter for fremstilling av Minoxidil er beskrevet for eksempel i Tysk patentpublikasjon DOS 1620649, US-patent 3910928, Finsk patent Fl 55194 og Finsk patentsøknad nr. 793307.
Den finske patentsøknad 793307 beskriver f.eks. en fremgangsmåte for fremstilling av Minoxidil, hvor 6-hydroksy-2,4-diaminopyrimidin omsettes med et sulfonylhalogenid med formel R-SO2-hal, hvor hal er halogen, til en forbindelse med formel
hvor R er en Ci-4-alkyl eller en fenylgruppe som eventuelt har opp til tre Ci - 4-alkylsubstituenter.
Denne forbindelse omsettes deretter med en persyre, for eksempel m-klorperbenzosyre for å gi en forbindelse med formel
som tilslutt omsettes med piperidin for å gi Minoxidil.
Den ovenfor beskrevne metode har imidlertid enkelte ulemper. Oksydasjonsmidlet m-klorperbenzosyre (m-CPBA) er en gift av 2. grad. Ved oksydasjon med denne forbindelse er det nødvendig å isolere oksydasjonsproduktet etter en heller komplisert og farlig metode: oppløsningsmidlet inndampes til tørrhet, residuet oppløses i en stor mengde etylacetat som ekstraheres flere ganger med en fortynnet natriumhydroksyd-oppløsning. Etylacetatet tørkes tilslutt og inndampes til et mindre volum hvorved produktet utfelles. Under oksydasjonen med m-CPBA inndampes således reaksjonsblandingen til tørrhet slik at det er en risiko for at eksplosive peroksyder dannes under oppvarmingen ved tørr tilstand. Dessuten gir oksydasjon med m-CPBA relativt store mengder biprodukter.
Vi har gjort det overraskende funn at de nevnte ulemper kan unngås dersom det i stedet for m-CPBA som oksydasjonsmiddel benyttes magnesium-monoperoksyftalat (MMPP), fortrinnsvis i form av heksahydratet som har formelen
Denne forbindelse er ikke klassifisert som et toksisk middel. Som faststoff er det en stabil forbindelse som ikke eksploderer ved oppvarming. Når oksydasjon foretas med dette middel kan oksydasjonsproduktet utfelles direkte fra den vandige oppløsningen.
Den kompliserte og farlige destillasjon til tørrhet kan således unngås. MMPP er en mer reaktiv oksydant enn m-CPBA, men danner likevel ikke i samme grad biprodukter. Dessuten er bruk av MMPP billigere enn m-CPBA.
Fremgangsmåten i henhold til vår oppfinnelse kan beskrives som følger:
I henhold til en foretrukket utførelsesform er R p-tolyl. Oksydasjonsproduktet som derved oppnås, 6-tosyloksy-2,4-diaminopyrimidin-3-oksyd, omsettes videre etter kjente fremgangsmåter til Minoxidil. Utgangsmaterialet, 6-(p-tolyl-sulfonyloksy)-2,4-diaminopyrimidin kan f.eks. fremstilles etter fremgangsmåten beskrevet i Finsk patentsøknad 793307.
Oksydasjonsreaksjonen kan foretas i forskjellige opp-løsningsmidler. Passende oppløsningsmidler er for eksempel alkoholer, fortrinnsvis lavere alkoholer, vandige oppløsninger av alkoholer, eddiksyre, aceton, tetrahydrofuran, en vandig oppløsning av metylenklorid og en faseoverførings-katalysator, DMF og DMSO. Et passende temperaturområde er fra 5 til 50°C, fortrinnsvis 15-30°C. Reaksjonen kan utføres i pH-området 4-9.
Fremgangsmåten i henhold til oppfinnelsen er beskrevet i det følgende.
Eksempel
a) 2,4-diamino-3-oksy-6-(p-tolylsulfonyloksy)pyrimidin
25 g (0,089 mol) 2,4-diamino-6-(p-tolylsulfonyloksy)-pyrimidin fremstillet etter fremgangsmåten beskrevet i Finsk patentsøknad 793307 (Eksempel 1, Trinn 1, Metode A), ble suspendert i en blanding av 200 ml aceton og 200 ml vann.
87,9 g (0,178 mol) magnesium-monoperoksyftalat-heksahydrat ble tilsatt til blandingen. Blandingen ble omrørt ved romtemperatur i 4 timer og tilsatt 250 ml vann, hvorpå blandingen ble omrørt ved en temperatur på 5-15°C i 1 time. Bunnfallet ble frafiltrert og vasket to ganger med 100 ml vann og én gang med 25 ml kald metanol. Det ble oppnådd 21 g (80%) 2,4-diamino-3-oksy-6-(p-tolylsulfonyloksy)pyrimidin. Smp. 128-129°C (dekomp.).
b) 2,4-diamino-3-oksy-6-piperidylpyrimidin
20 g (0,067 mol) 2,4-diamino-3-oksy-6-(p-tolylsulfonyl-oksy ) pyrimidin fra foregående trinn og 140 ml piperidin ble oppvarmet til 80-90°C i 2 timer. Piperidinet ble avdestillert i vakuum. Residuet ble tilsatt 50 ml av en 5% oppløsning av natriumhydroksyd i vann og 50 ml toluen, hvorpå blandingen ble omrørt ved 20-25°C i 1/2 time. Blandingen ble filtrert og bunnfallet vasket to ganger med 30 ml vann og én gang med 30 ml toluen. Det ble oppnådd 8,4 g (60%) 2,4-diamino-3-oksy-6-piperidylpyrimidin. Smp. 255-260°C (dekomp.).
Claims (2)
1. Fremgangsmåte for fremstilling av 2,4-diamino-3-oksy-6-piperidylpyrimidin eller Minoxidil, hvor en forbindelse med formel
hvor R er en Ci-4 -alkyl eller en fenylgruppe som eventuelt har opp til tre Ci - 4-alkylsubstituenter, oksyderes til en forbindelse med formel
som etter kjente fremgangsmåter omsettes med piperidin til Minoxidil, karakterisert ved at magnesium-monoperoksyftalat (MMPP) som har formelen
benyttes som oksydasjonsmiddel.
2. Fremgangsmåte ifølge krav 1, karakterisert ved at det fremstilles en forbindelse hvor R er p-tolyl.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI864046A FI864046A7 (fi) | 1986-10-07 | 1986-10-07 | Menetelmä terapeuttisesti aktiivisen yhdisteen valmistamiseksi. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO872810D0 NO872810D0 (no) | 1987-07-06 |
| NO872810L true NO872810L (no) | 1988-04-08 |
Family
ID=8523270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO872810A NO872810L (no) | 1986-10-07 | 1987-07-06 | Fremgangsmaate for fremstilling av en terapeutisk aktiv forbindelse. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4866174A (no) |
| EP (1) | EP0270201B1 (no) |
| JP (1) | JPS6396175A (no) |
| KR (1) | KR880005095A (no) |
| AT (1) | ATE61584T1 (no) |
| AU (1) | AU590431B2 (no) |
| CA (1) | CA1268766A (no) |
| DE (1) | DE3768617D1 (no) |
| DK (1) | DK348687A (no) |
| ES (1) | ES2021048B3 (no) |
| FI (2) | FI864046A7 (no) |
| FR (1) | FR2604707B1 (no) |
| HU (1) | HUT44533A (no) |
| IL (1) | IL83351A0 (no) |
| NO (1) | NO872810L (no) |
| NZ (1) | NZ221011A (no) |
| PT (1) | PT85392B (no) |
| ZA (1) | ZA875174B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI871773A0 (fi) * | 1987-04-22 | 1987-04-22 | Farmos Oy | Foerfarande foer framstaellning av en terapeutiskt aktiv foerening. |
| FR2636840B1 (fr) * | 1988-09-23 | 1990-12-21 | Norchim Sarl | Sel du 6-piperidino-2,4-diaminopyrimidine-3-oxyde et de l'acide aceturique, leur preparation et leur application dermatocosmetologiques |
| NZ244301A (en) * | 1991-09-20 | 1994-08-26 | Merck & Co Inc | Preparation of 2-pyridylmethylsulphinylbenzimidazole and pyridoimidazole derivatives from the corresponding sulphenyl compounds |
| FR2697251B1 (fr) * | 1992-10-22 | 1994-12-02 | Synthelabo | N-oxydes de dérivés de 1-(4-chlorophényl)-2-[4-[(4-fluorophényl)méthyl] pipéridin-1-yl]éthanol, leur procédé de préparation et leur application en thérapeutique. |
| CN117247357A (zh) * | 2023-09-20 | 2023-12-19 | 吉林大学 | 一种米诺地尔的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3644364A (en) * | 1970-03-31 | 1972-02-22 | Upjohn Co | Compounds and process |
| US3998827A (en) * | 1971-04-07 | 1976-12-21 | The Upjohn Company | 6-amino-4-(substituted piperidino)-1,2-dihydro-1-hydroxy-2-iminopyrimidines |
| HU177601B (en) * | 1978-10-27 | 1981-11-28 | Egyt Gyogyszervegyeszeti Gyar | New process for preparing 6-piperidino-2,4-diamino-pyrimidine-3-oxide |
| EP0027693B2 (en) * | 1979-10-18 | 1988-05-11 | Interox Chemicals Limited | Magnesium salts of peroxycarboxylic acids, processes for their preparation and their use as bleaching agents in washing compositions, and processes |
| US4483781A (en) * | 1983-09-02 | 1984-11-20 | The Procter & Gamble Company | Magnesium salts of peroxycarboxylic acids |
-
1986
- 1986-10-07 FI FI864046A patent/FI864046A7/fi not_active Application Discontinuation
-
1987
- 1987-06-16 FR FR8708342A patent/FR2604707B1/fr not_active Expired
- 1987-07-06 NO NO872810A patent/NO872810L/no unknown
- 1987-07-07 DK DK348687A patent/DK348687A/da unknown
- 1987-07-09 NZ NZ221011A patent/NZ221011A/xx unknown
- 1987-07-10 AU AU75517/87A patent/AU590431B2/en not_active Ceased
- 1987-07-13 US US07/072,725 patent/US4866174A/en not_active Expired - Fee Related
- 1987-07-15 ZA ZA875174A patent/ZA875174B/xx unknown
- 1987-07-16 EP EP87306305A patent/EP0270201B1/en not_active Expired - Lifetime
- 1987-07-16 ES ES87306305T patent/ES2021048B3/es not_active Expired - Lifetime
- 1987-07-16 AT AT87306305T patent/ATE61584T1/de active
- 1987-07-16 DE DE8787306305T patent/DE3768617D1/de not_active Expired - Lifetime
- 1987-07-23 PT PT85392A patent/PT85392B/pt unknown
- 1987-07-27 IL IL83351A patent/IL83351A0/xx unknown
- 1987-07-28 KR KR1019870008195A patent/KR880005095A/ko not_active Withdrawn
- 1987-08-19 HU HU873719A patent/HUT44533A/hu unknown
- 1987-09-01 CA CA000545907A patent/CA1268766A/en not_active Expired - Fee Related
- 1987-09-11 FI FI873933A patent/FI78910C/fi not_active IP Right Cessation
- 1987-10-06 JP JP62252299A patent/JPS6396175A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ATE61584T1 (de) | 1991-03-15 |
| AU7551787A (en) | 1988-04-14 |
| ES2021048B3 (es) | 1991-10-16 |
| FI864046A0 (fi) | 1986-10-07 |
| FI864046L (fi) | 1988-04-08 |
| KR880005095A (ko) | 1988-06-28 |
| PT85392A (en) | 1987-08-01 |
| FI78910C (fi) | 1989-10-10 |
| DK348687D0 (da) | 1987-07-07 |
| EP0270201B1 (en) | 1991-03-13 |
| DK348687A (da) | 1988-04-08 |
| JPS6396175A (ja) | 1988-04-27 |
| NZ221011A (en) | 1990-05-28 |
| US4866174A (en) | 1989-09-12 |
| ZA875174B (en) | 1988-01-20 |
| FI873933A0 (fi) | 1987-09-11 |
| EP0270201A1 (en) | 1988-06-08 |
| CA1268766A (en) | 1990-05-08 |
| AU590431B2 (en) | 1989-11-02 |
| FR2604707B1 (fr) | 1989-06-09 |
| IL83351A0 (en) | 1987-12-31 |
| FR2604707A1 (fr) | 1988-04-08 |
| NO872810D0 (no) | 1987-07-06 |
| FI864046A7 (fi) | 1988-04-08 |
| FI873933L (fi) | 1988-04-08 |
| FI78910B (fi) | 1989-06-30 |
| HUT44533A (en) | 1988-03-28 |
| DE3768617D1 (de) | 1991-04-18 |
| PT85392B (en) | 1990-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1340960C (en) | Chroman derivatives | |
| AU652238B2 (en) | Sulfonamides and their medical use | |
| AU653604B2 (en) | Novel sulfonamides | |
| EP0824524B1 (en) | Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as inhibitors of viral reverse transcriptase | |
| CA2110944A1 (en) | Novel sulfonamides | |
| WO2010077062A2 (en) | Preparation method of statin compound and benzothiazolyl sulfone compound used therein | |
| NO140069B (no) | Pulverformet, lagringsbestandig vaskemiddelblanding | |
| CN104994855B (zh) | 制备逆转录酶抑制剂的方法 | |
| EP0270201B1 (en) | A method for the preparation of a 2,4-diamino-3-oxy-pyrimidine derivative | |
| KR100654265B1 (ko) | 4-(헤테로아릴-메틸)-할로겐-1(2ｈ)-프탈라지논의 제조 방법 | |
| JP3156026B2 (ja) | ホスホン酸ジエステル誘導体 | |
| HU196207B (en) | Process for preparing 9-/2-hydroxy-ethoxy/-methyl-guanine | |
| DK152674B (da) | Analogifremgangsmaade til fremstilling af 3-metyltiometyl-4-oxo-quinolonderivater | |
| HU219231B (en) | N-5-protected 2,5-diamino-4,6-dichloro-pyrimidine derivatives , process for producing them and intermediates | |
| NO147838B (no) | Mellomprodukt til bruk ved fremstilling av det hypotensive middel 2-(4-(2-furoyl)piperazin-1-yl)-4-amino-6,7-dimetoksykinazolin | |
| US3180866A (en) | Substituted sulfapyrimidine derivatives | |
| HU177601B (en) | New process for preparing 6-piperidino-2,4-diamino-pyrimidine-3-oxide | |
| RU2837452C1 (ru) | Способ синтеза противоопухолевого соединения и его промежуточных соединений | |
| SU1117298A1 (ru) | Способ получени производного урацила | |
| JP3013778B2 (ja) | ベンゼンスルホンアミド誘導体及びその製法 | |
| DK148082B (da) | Analogifremgangsmaade til fremstilling af 1-ethyl-1,4-dihydro-6-(2-naphthyl)-4-oxo-nicotinsyrederivater | |
| IL23556A (en) | 2-Sulfonamido pyrimidines are converted instead of 5 | |
| AU2003200847A1 (en) | Process and intermediates for pyridazinone antidiabetic agents | |
| HU198949B (en) | Process for producing 5-substituted-3'azido-2',3'-dideoxyribonucleosides | |
| JPS6031832B2 (ja) | １−（２′−テトラヒドロフリル）−５−フルオロウラシルの製造法 |