NO152298B - Fremgangsmaate til fremstilling av 6,7-dimetoksy-4-amino-2-(4-(furoyl)-1-piperazinyl)-kinazolin-hydroklorid - Google Patents
Fremgangsmaate til fremstilling av 6,7-dimetoksy-4-amino-2-(4-(furoyl)-1-piperazinyl)-kinazolin-hydroklorid Download PDFInfo
- Publication number
- NO152298B NO152298B NO794279A NO794279A NO152298B NO 152298 B NO152298 B NO 152298B NO 794279 A NO794279 A NO 794279A NO 794279 A NO794279 A NO 794279A NO 152298 B NO152298 B NO 152298B
- Authority
- NO
- Norway
- Prior art keywords
- furoyl
- hydrochloride
- piperazinyl
- amino
- formula
- Prior art date
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- -1 4- (FUROYL) -1-PIPERAZINYL Chemical class 0.000 title description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims 1
- VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 239000000047 product Substances 0.000 description 8
- 229960001289 prazosin Drugs 0.000 description 6
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 6
- WFXFYZULCQKPIP-UHFFFAOYSA-N prazosin hydrochloride Chemical compound [H+].[Cl-].N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 WFXFYZULCQKPIP-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 229960002386 prazosin hydrochloride Drugs 0.000 description 5
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical class 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 description 1
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Cephalosporin Compounds (AREA)
Description
Oppfinnelsen angår en fremgangsmåte til fremstilling av 6,7-dimetoksy-4-amino-2- [4-(2-furoyl)-l-piperazinyljkinazolin-hydroklorid/ dvs. prazosinhydroklorid, med blodtrykksenkende virk-ning og formelen
Tidligere kjente metoder til fremstilling av prazosin er beskrevet i bl.a. US patentskrift nr. 3 511 836, NL patentsøknad nr.
72 06067 og publisert DE patentsøknad nr. 24 57 911.
De praktiske utførelser av disse kjente fremgangsmåter er imidlertid forbundet med mange vanskeligheter. Dessuten er utbyttet ved disse fremgangsmåter temmelig lavt og rensingen av den utvunnede forbindelse er besværlig. Ved den metode til. fremstilling av prazosin som er beskrevet i NO utlegningsskrift nr. 147 244 har man kunnet redusere merkbart de forstyrrende fak-torer som inntreffer ved de tidligere kjente metoder og samtidig oppnå et bedre utbytte.
Ved fremgangsmåten til fremstilling av prazosin ifølge
No utlegningsskrift 147 244 utføres lukkingen av kinazolinringen intramolekylært under anvendelse av metyl-N-(3,4-dimetoksy-6-cyanofenyl)-£4-(2-furoyl)-1-piperazinylJ-tioformamidat med den nedenfor angitte formel III som utgangsmateriale. Denne forbindelse omsettes med ammoniakk i formamid i nærvær av en basisk katalysator, f.eks. natriumamid, i henhold til følgende reak-sj onsformel:
Utbyttet av prazosin ved denne fremgangsmåte beløper seg til 40-50% råprodukt med en irenhetsgrad på 95-97%. Produktet må deretter dessuten omsettes til hydrokloridet som utgjør det egentlige legemiddel, samt rekrystalliseres noen ganger før man oppnår den renhetsgrad som kreves for legemidler (99,7-99,8%). Det totale utbytte synker derved til ca. 35%.
Det er nå overraskende funnet at utbyttet av prazosin og samtidig produktets renhetsgrad kan forbedres betraktelig og fremstillings- og rengjøringsmetodene forenkles dersom man i den ovenfor angitte reaksjon for lukking av kinazolinringen ifølge oppfinnelsen anvender et stort overskudd ammoniumklorid isteden-for ammoniakkgass. Ved utførelse av reaksjonen kreves derved ingen basisk katalysator (natriumamid o.l.). Ved reaksjonen dannes dessuten det ønskede prazosinhydroklorid med godt utbytte (93-95%). Renhetsgraden av råproduktet er dessuten meget høy, ca. 99,5%. Ved en enkelt rekrystallisering av dette råprodukt oppnås den nødven-dige renhetsgrad på (99,7-99,8%). Det totale utbytte i dette til-felle er 85-86%.
Ved fremstilling av prazosinhydroklorid ifølge oppfinnelsen oppnår man således en meget betydelig forbedring sammenlignet med tidligere kjente metoder. Den praktiske gjennomføring av reaksjonen, isoleringen og rengjøringen av produktet blir vesentlig enklere enn tidligere. Dessuten eliminerer man bruken av natrium-amidet som er vanskelig å håndtere i større mengder.
Ved anvendelse av ammoniakk og natriumamid skjer reaksjonen i alkalisk miljø, hvorved der som følge av det som oppløsnings-middel anvendte formamids innvirkning skjer en viss substitusjon med en formylgruppe av den i prazosinmolekylet inngående furoyl-gruppe. Ammoniumkloridoppløsningen derimot er svakt sur og derfor skjer det nesten ingen omacylering. Dette er en fordel da det har vist seg vanskelig i praksis å fjerne fullstendig den nevnte for-urensning som dannes i små mengder.
Det som utgangsmateriale anvendte metyl-N-(3,4-dimetoksy-6-cyanofenyl)- ^4-(2-furoyl)-1-piperazinylJtioformamidat (III)
kan fremstilles med et utbytte på 90 % ved omsetning av den tilsvarende ikke metylerte forbindelse med formel II med metyl-jodid slik det er beskrevet i NO utlegningsskrift nr. 147 244.
Det følgende eksempel illustrerer oppfinnelsen.
Eksempel 6 , 7-dimetoksy-4-amino-2- |^4- (2-furoyl) -1-piperazinylJ kinazolin-hydroklorid
275 g (0,66 mol) metyl-N-(3,4-dimetoksy-6-cyanofenyl-^4-(2-furoyl-1-piperazinylJtioformamidat løses opp i 3000 ml formamid, og 1375 g (25,7 mol) ammoniumklorid tilsettes under omrøring. Reaksjonsblandingen oppvarmes deretter under omrøring i 15-20 timer ved 120°C samtidig som nitrogengass føres inn for bort-ledning av den metantiol som dannes (kan absorberes i natrium-hypokloritt-oppløsning). Det dannede prazosinhydroklorid utkry-stalliseres etterhvert fra reaksjonsblandingen. Etter at reaksjonen er ferdig tilsettes 3-4 kg is. Produktet filtreres/ vaskes med kaldt vann og aceton og tørkes. Utbyttet er 254-259 g (93-95%) og renhetsgraden 99,5% (HPLC). Produktet rekrystalliseres fra en vann/etanol-blanding på ca. 10 1 (15:50). Utbyttet er 232-235 g (85-86%), renhetsgraden 99,7-99,8% (HPLC). Produktets IR-, NMR- og massespektre er nøyaktig tilsvarende spektre for prazosinhydroklorid som er fremstilt ved de fra litteraturen kjente metoder som er angitt ovenfor.
Claims (3)
1. Fremgangsmåte til fremstilling av 6,7-dimetoksy-4-amino-2-^4-(2-furoyl)-1-piperazinyl] kinazolinhydroklorid med formelen
idet der med utgangspunkt i metyl-N- (3,4-dimetoksy-6- cyanofenyl) - jj4- (2-furoyl)-l-piperazinylJ tiof ormamidat med formelen utføres en intramolekylær lukking av kinazolinringen, karakterisert ved at forbindelsen med formel III omsettes ved høy temperatur med et stort overskudd av ammoniumklorid i et polært oppløsningsmiddel.
2. Fremgangsmåte som angitt i krav 1,karakterisertved at der anvendes 30-40 mol NH^Cl pr. mol forbindelse med formel III.
3. Fremgangsmåte som angitt i krav 1 eller 2,karakterisert ved at reaksjonen utføres i formamid som oppløs-ningsmiddel ved en temperatur på 100-140°C, fortrinnsvis 120°C og med en reaksjonstid på 15-20 timer.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI790320A FI67699C (fi) | 1979-01-31 | 1979-01-31 | Foerfarande foer framstaellning av 6,7-dimetoxi-4-amino-2-(4-(2-furoyl)-1-piperazinyl)kinazolinhydroklorid med blodtryckssaenkande verkan |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO794279L NO794279L (no) | 1980-08-01 |
| NO152298B true NO152298B (no) | 1985-05-28 |
| NO152298C NO152298C (no) | 1985-09-04 |
Family
ID=8512343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO794279A NO152298C (no) | 1979-01-31 | 1979-12-27 | Fremgangsmaate til fremstilling av 6,7-dimetoksy-4-amino-2-(4-(furoyl)-1-piperazinyl)-kinazolin-hydroklorid |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4271300A (no) |
| JP (1) | JPS55104280A (no) |
| AT (1) | AT374475B (no) |
| BE (1) | BE881297A (no) |
| CA (1) | CA1128945A (no) |
| CH (1) | CH644605A5 (no) |
| CS (1) | CS214692B2 (no) |
| DD (1) | DD148952A1 (no) |
| DE (1) | DE3002553A1 (no) |
| DK (1) | DK158352C (no) |
| FI (1) | FI67699C (no) |
| FR (1) | FR2447920A1 (no) |
| GB (1) | GB2041932B (no) |
| HU (1) | HU181016B (no) |
| NL (1) | NL190701C (no) |
| NO (1) | NO152298C (no) |
| PL (1) | PL126994B1 (no) |
| SE (1) | SE430692B (no) |
| SU (1) | SU900812A3 (no) |
| YU (1) | YU41498B (no) |
| ZA (1) | ZA80501B (no) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI70411C (fi) * | 1980-12-29 | 1986-09-19 | Pfizer | Foerfarande foer framstaellning av nya antihypertensiva 4-amino-6,7-dimetoxi-2-piperazinokinazolin derivat |
| FI79107C (fi) * | 1984-06-25 | 1989-11-10 | Orion Yhtymae Oy | Foerfarande foer framstaellning av stabil -form av prazosinhydroklorid. |
| US4601897A (en) * | 1985-11-06 | 1986-07-22 | Pfizer Inc. | Prazosin-pirbuterol combination for bronchodilation |
| AT384218B (de) * | 1985-12-04 | 1987-10-12 | Gerot Pharmazeutika | Verfahren zur herstellung von neuen chinazolin-derivaten |
| YU70890A (en) * | 1989-04-21 | 1992-05-28 | Egyt Gyogyszervegyeszeti Gyar | Process for obtaining quinazoline derivatives |
| CA2077252C (en) * | 1992-08-31 | 2001-04-10 | Khashayar Karimian | Methods of making ureas and guanidines, and intermediates therefor |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
| GB1390015A (en) * | 1971-05-07 | 1975-04-09 | Koninklijke Pharma Fab Nv | 4-amino-quinazoline compounds |
| US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
| US4092315A (en) * | 1976-03-01 | 1978-05-30 | Pfizer Inc. | Novel crystalline forms of prazosin hydrochloride |
| FI58125C (fi) * | 1976-12-15 | 1985-01-02 | Orion Yhtymae Oy | Foerfarande foer framstaellning av 6,7-dimetoxi-4-amino-2-(4-(2-furoyl)-1-piperazinyl)kinazolin med blodtryckssaenkande vekan |
| FI58124C (fi) * | 1976-12-15 | 1980-12-10 | Orion Yhtymae Oy | Ny mellanprodukt 3,4-dimetoxi-6-(4-(2-furoyl)-1-piperazinyltiokarbamido)-bensonitril foer framstaellning av 6,7-dimetoxi-4-amino-2-(4-(2-furoyl)-1-piperazinyl)kinazolin med blodtryckssaenkande verkan |
-
1979
- 1979-01-31 FI FI790320A patent/FI67699C/fi not_active IP Right Cessation
- 1979-12-27 NO NO794279A patent/NO152298C/no unknown
-
1980
- 1980-01-09 CA CA343,361A patent/CA1128945A/en not_active Expired
- 1980-01-09 CH CH12180A patent/CH644605A5/de not_active IP Right Cessation
- 1980-01-09 US US06/110,589 patent/US4271300A/en not_active Expired - Lifetime
- 1980-01-10 YU YU58/80A patent/YU41498B/xx unknown
- 1980-01-15 AT AT0019580A patent/AT374475B/de not_active IP Right Cessation
- 1980-01-16 NL NL8000289A patent/NL190701C/xx not_active IP Right Cessation
- 1980-01-23 BE BE0/199070A patent/BE881297A/fr not_active IP Right Cessation
- 1980-01-25 DE DE19803002553 patent/DE3002553A1/de active Granted
- 1980-01-28 ZA ZA00800501A patent/ZA80501B/xx unknown
- 1980-01-28 CS CS80588A patent/CS214692B2/cs unknown
- 1980-01-29 HU HU8080182A patent/HU181016B/hu not_active IP Right Cessation
- 1980-01-29 GB GB8002903A patent/GB2041932B/en not_active Expired
- 1980-01-30 SU SU802874898A patent/SU900812A3/ru active
- 1980-01-30 FR FR8001991A patent/FR2447920A1/fr active Granted
- 1980-01-30 PL PL1980221684A patent/PL126994B1/pl unknown
- 1980-01-30 JP JP1081580A patent/JPS55104280A/ja active Granted
- 1980-01-31 DK DK042680A patent/DK158352C/da not_active IP Right Cessation
- 1980-01-31 SE SE8000777A patent/SE430692B/sv unknown
- 1980-01-31 DD DD80218776A patent/DD148952A1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DD148952A1 (de) | 1981-06-17 |
| GB2041932A (en) | 1980-09-17 |
| AT374475B (de) | 1984-04-25 |
| FI67699C (fi) | 1985-05-10 |
| ZA80501B (en) | 1981-02-25 |
| PL126994B1 (en) | 1983-09-30 |
| SU900812A3 (ru) | 1982-01-23 |
| JPS55104280A (en) | 1980-08-09 |
| CA1128945A (en) | 1982-08-03 |
| SE8000777L (sv) | 1980-08-01 |
| YU5880A (en) | 1983-02-28 |
| JPS6310955B2 (no) | 1988-03-10 |
| HU181016B (en) | 1983-05-30 |
| US4271300A (en) | 1981-06-02 |
| DK42680A (da) | 1980-08-01 |
| SE430692B (sv) | 1983-12-05 |
| ATA19580A (de) | 1983-09-15 |
| DE3002553C2 (no) | 1988-10-27 |
| NL190701C (nl) | 1994-07-01 |
| GB2041932B (en) | 1982-10-27 |
| NL190701B (nl) | 1994-02-01 |
| NO794279L (no) | 1980-08-01 |
| DE3002553A1 (de) | 1980-08-07 |
| CH644605A5 (de) | 1984-08-15 |
| NO152298C (no) | 1985-09-04 |
| FR2447920A1 (fr) | 1980-08-29 |
| DK158352B (da) | 1990-05-07 |
| NL8000289A (nl) | 1980-08-04 |
| DK158352C (da) | 1990-10-08 |
| FR2447920B1 (no) | 1982-12-03 |
| BE881297A (fr) | 1980-05-16 |
| YU41498B (en) | 1987-08-31 |
| FI67699B (fi) | 1985-01-31 |
| FI790320A (fi) | 1980-08-01 |
| CS214692B2 (en) | 1982-05-28 |
| PL221684A1 (no) | 1980-10-20 |
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