CS214692B2 - Method of making the hydrochloride of 6,7-dimethoxy-4-amino-2-+l4-+l2-furoyl+p-1-piperazinyl+pchnazoline - Google Patents
Method of making the hydrochloride of 6,7-dimethoxy-4-amino-2-+l4-+l2-furoyl+p-1-piperazinyl+pchnazoline Download PDFInfo
- Publication number
- CS214692B2 CS214692B2 CS80588A CS58880A CS214692B2 CS 214692 B2 CS214692 B2 CS 214692B2 CS 80588 A CS80588 A CS 80588A CS 58880 A CS58880 A CS 58880A CS 214692 B2 CS214692 B2 CS 214692B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- dimethoxy
- piperazinyl
- hydrochloride
- furoyl
- amino
- Prior art date
Links
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 235000019270 ammonium chloride Nutrition 0.000 claims abstract description 6
- 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
- -1 3,4-dimethoxy-6-cyanophenyl Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
- 230000003276 anti-hypertensive effect Effects 0.000 claims 1
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 claims 1
- 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
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound 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 claims 1
- 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 abstract description 6
- 239000000047 product Substances 0.000 description 7
- 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 3
- 229960002386 prazosin hydrochloride Drugs 0.000 description 3
- 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BJAYMNUBIULRMF-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzonitrile Chemical compound COC1=CC(N)=C(C#N)C=C1OC BJAYMNUBIULRMF-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000003513 alkali Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007363 ring formation reaction 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
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Furan Compounds (AREA)
- Cephalosporin Compounds (AREA)
Description
Dosud známé způsoby - výroby - jsou popsané v těchto patentech: US-patent číslo 5 511 -836, NL-patent č. 72 06067 a -DT-patent č. 2 457 911.
Avšak při praktickém provedení popsaných způsobů se vyskytuje řada technických těžkostí. Kromě toho při použití těchto způsobů je výtěžek příliš nízký a čištění produktu je pracné. Při způsobu výroby prazosinu popsaném v československém patentu č. 197 312 se nevýhody vyskytující se u dřívějších postupů významně snižují a zároveň dochází ke zvýšení výtěžku.
Způsobem výroby prazosinu podle československého patentu č. 197 312 se uzavření
X chinazolinového kruhu provádí intramolekulárně za použití výchozího methyl-N-(3,4-dimethoxy-6-kyanof enyl )-(4-( 2-f uroyl ' ) -1-piperazinyljthioformamidátu vzorce II. Tato sloučenina se nechá reagovat s amoniakem ve formamidu v přítomnosti alaklického katalyzátoru, jako natriumamidu, podle následujícího· reakčního schématu:
prazosin
Při tomto způsobu výtěžek prazosinu je 40 až 50- !°/o a surový produkt má čistotu 95 až 97 - %. Potom se produkt musí ještě převést na hydrochlorid, který - působí jako vlastní léčivo a musí se několikrát krystalovat předtím, než se dosáhne -čistoty požadované u lékárnického zboží (99,7 až
99,8 %). Celkový- výtěžek přitom - klesne asi na 35 -%.
Nyní bylo s překvapením objeveno, že výtěžek prazosinu a současně čistota tohoto produktu se mohou značně zvýšit a výrobní a čisticí postup se může zjednodušit, použije-li se při shora uvedeném reakčním uzavření chinazolinového kruhu velký přebytek chloridu amonného, jak je uvedeno v tomto vynálezu, místo aby se použilo plynného amoniaku. V tomto případě к provedení reakce není zapotřebí alkalického katalyzátoru (natriumamidu a podobně). Kromě toho se požadovaný prazosinhydrochlorid tvoří přímo při reakci v dobrém výtěžku (93 až 95 %). Čistota surového produktu je také velmi vysoká, okolo 99,5 °/o. Požadovaný stupeň čistoty (99,7 až 99,8 % ) se dosahuje jednoduchou krystalizací tohoto surového produktu. Celkový výtěžek je v tomto případě 85 až 86 %.
Způsob výroby prazosinhydrochloridu podle vynálezu tak představuje velmi pozoruhodné zlepšení proti dřívějším postupům. Praktické provedení reakce a oddělení a čištění produktu jsou značně zjednodušeny. Kromě toho se vylučuje použití natriumamidu, se kterým se ve větším množství obtížně pracuje.
Při použití amoniaku a natriumamidu probíhá reakce v alkalickém prostředí, přičemž do určité míry nastává náhrada furoylové skupiny přítomné v molekule prazosinu formylovou skupinou, к čemuž dochází působením formamidu použitého jako rozpouštědlo. Naproti tomu roztok chloridu amonného jo slabě kyselý a ke změně kyselosti stěží dochází. Úplné vyloučení nečistoty vznikající v malé koncentraci se v praxi ukázalo obtížné. Methyl-N-(3,4-dime thoxy-6-kyanof enyl)- [ 4-(2-f uroyl) -1-piperazinyljthioformamidát vzorce II se může vyrobit v 70 až 75% výtěžku reakcí 3,4-dimethoxy-6-aminobenzonitrilu s methyljodidem způsobem, který je popsán v československém patentu č. 195 347.
Následující příklad ilustruje vynález.
Příklad
Hydrochlorid 6,7-dimethoxy-4-amino-2- [ 4- (2-furoiyl) -l-piperaziny 1 ] chinazo-linu
275 g (0,66 mol) methyl-N-(3,4-dimethoxy-6-kyanof enyl )-(4-( 2-f uroyl ) -1-piperazinyl]thioformamidátu se rozpustí v 3 000 ml formamidu a za míchání přidá 1 375 g (27,5 mol) chloridu amonného. Potom se reakční směs zahřívá 15 až 20 hodin na teplotu 120 °C za míchání a také probublávání plynným dusíkem, к odstranění vzniklého methylmerkaptanu (ten se může absorbovat v roztoku chlornanu sodného). Vyrobený prazosinhydrochlorid postupně vykrystaluje z reakční směsi. Po ukončení reakce se ke směsi přidají 3 až 4 kg ledu. Produkt se odfiltruje, promyje studenou vodou a acetonem a suší. Výtěžek je 254 až 259 g (93 až 95 %). Čistota: 99,5 % (HPLC). Produkt se nechá krystalovat asi z 10 litrů směsi vody a ethanolu v poměru 15 : 50. Výtěžek je 232 až 235 g (85 až 86 %). Čistota: 99,7 až 99,8 % (HPLC). IČ, NMR a hmotnostní spektrum produktu jsou identické s odpovídajícími spektry prazosinhydrochloridu vyrobeného metodami dříve popsanými v literatuře^.
Claims (3)
1. Způsob výroby hydrochloridu 6,7-dimethoxy-4-amino-2- [ 4- (2-f uroyl) -1-piperazinyljchinazolinu s antihypertenzívním účinkem vzorce I z methyl-N- (3,4-dimethoxy-6-kyanofenyl) - [ 4- (2-f uroyl) -1-piperazinyl ] thiof ormamídátu vzorce II intramolekulárním uzavřením chinazolinového kruhu, vyznačující se tím, že se sloučenina vzorce II nechá reagovat při teplotě 100 až 140 °C s velkým přebytkem chloridu amonného v polárním rozpouštědle.
2. Způsob podle bodu 1 vyznačující se tím, že se chlorid amonný používá v poměru 30 až 40 molů NH4C1 na 1 mol sloučeniny vzorce II.
3. Způsob podle bodu 1 nebo 2 vyznačující se tím, že· se reakce provádí ve formamidu, jako rozpouštědle, při teplotě 100 až 140 °C, s výhodou při 120 °C, po dobu 15 až 20 hodin.
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 (1)
| Publication Number | Publication Date |
|---|---|
| CS214692B2 true CS214692B2 (en) | 1982-05-28 |
Family
ID=8512343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS80588A CS214692B2 (en) | 1979-01-31 | 1980-01-28 | Method of making the hydrochloride of 6,7-dimethoxy-4-amino-2-+l4-+l2-furoyl+p-1-piperazinyl+pchnazoline |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4271300A (cs) |
| JP (1) | JPS55104280A (cs) |
| AT (1) | AT374475B (cs) |
| BE (1) | BE881297A (cs) |
| CA (1) | CA1128945A (cs) |
| CH (1) | CH644605A5 (cs) |
| CS (1) | CS214692B2 (cs) |
| DD (1) | DD148952A1 (cs) |
| DE (1) | DE3002553A1 (cs) |
| DK (1) | DK158352C (cs) |
| FI (1) | FI67699C (cs) |
| FR (1) | FR2447920A1 (cs) |
| GB (1) | GB2041932B (cs) |
| HU (1) | HU181016B (cs) |
| NL (1) | NL190701C (cs) |
| NO (1) | NO152298C (cs) |
| PL (1) | PL126994B1 (cs) |
| SE (1) | SE430692B (cs) |
| SU (1) | SU900812A3 (cs) |
| YU (1) | YU41498B (cs) |
| ZA (1) | ZA80501B (cs) |
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 |
| GB1390014A (en) * | 1971-05-07 | 1975-04-09 | Koninklijke Pharma Fab Nv | Process for the preparation of carbocyclic fused pyrimidine derivatives |
| 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 |
| 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 |
| 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 |
-
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 US US06/110,589 patent/US4271300A/en not_active Expired - Lifetime
- 1980-01-09 CH CH12180A patent/CH644605A5/de not_active IP Right Cessation
- 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 CS CS80588A patent/CS214692B2/cs unknown
- 1980-01-28 ZA ZA00800501A patent/ZA80501B/xx 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 JP JP1081580A patent/JPS55104280A/ja active Granted
- 1980-01-30 FR FR8001991A patent/FR2447920A1/fr active Granted
- 1980-01-30 PL PL1980221684A patent/PL126994B1/pl unknown
- 1980-01-30 SU SU802874898A patent/SU900812A3/ru active
- 1980-01-31 SE SE8000777A patent/SE430692B/sv unknown
- 1980-01-31 DK DK042680A patent/DK158352C/da not_active IP Right Cessation
- 1980-01-31 DD DD80218776A patent/DD148952A1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI67699B (fi) | 1985-01-31 |
| SE430692B (sv) | 1983-12-05 |
| CA1128945A (en) | 1982-08-03 |
| FI67699C (fi) | 1985-05-10 |
| US4271300A (en) | 1981-06-02 |
| NO794279L (no) | 1980-08-01 |
| SE8000777L (sv) | 1980-08-01 |
| GB2041932B (en) | 1982-10-27 |
| YU5880A (en) | 1983-02-28 |
| NO152298C (no) | 1985-09-04 |
| BE881297A (fr) | 1980-05-16 |
| DE3002553A1 (de) | 1980-08-07 |
| YU41498B (en) | 1987-08-31 |
| ATA19580A (de) | 1983-09-15 |
| DE3002553C2 (cs) | 1988-10-27 |
| CH644605A5 (de) | 1984-08-15 |
| FR2447920B1 (cs) | 1982-12-03 |
| DK42680A (da) | 1980-08-01 |
| HU181016B (en) | 1983-05-30 |
| NL190701B (nl) | 1994-02-01 |
| FI790320A (fi) | 1980-08-01 |
| NL8000289A (nl) | 1980-08-04 |
| PL126994B1 (en) | 1983-09-30 |
| ZA80501B (en) | 1981-02-25 |
| JPS55104280A (en) | 1980-08-09 |
| AT374475B (de) | 1984-04-25 |
| JPS6310955B2 (cs) | 1988-03-10 |
| NO152298B (no) | 1985-05-28 |
| DK158352B (da) | 1990-05-07 |
| SU900812A3 (ru) | 1982-01-23 |
| DD148952A1 (de) | 1981-06-17 |
| NL190701C (nl) | 1994-07-01 |
| DK158352C (da) | 1990-10-08 |
| GB2041932A (en) | 1980-09-17 |
| FR2447920A1 (fr) | 1980-08-29 |
| PL221684A1 (cs) | 1980-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7262304B2 (en) | One-pot process for the preparation of 1,2-benzisoxazole-3-methanesulfonamide | |
| FI59991B (fi) | Foerfarande foer framstaellning av 2-arylamino-2-imidazolin-derivat och deras salter | |
| CS214692B2 (en) | Method of making the hydrochloride of 6,7-dimethoxy-4-amino-2-+l4-+l2-furoyl+p-1-piperazinyl+pchnazoline | |
| US6197998B1 (en) | Process for producing N-glycyltyrosine and its crystal structure | |
| SU677657A3 (ru) | Способ получени -формилированных соединений | |
| KR101276667B1 (ko) | 3,4-디클로로이소티아졸카복실산의 제조방법 | |
| CN112272665B (zh) | 制备立他司特的方法 | |
| KR20010005943A (ko) | 0-(3-아미노-2-히드록시-프로필)-히드록심산할라이드의 제조방법 | |
| US5395945A (en) | Synthesis of 3,3-dinitroazetidine | |
| EP0131472B1 (en) | 5-mercapto-1,2,3-thiadiazoles composition and process for preparing the same | |
| EP0070467B1 (en) | Process for synthesising n-isopropyl-n'-o-carbomethoxyphenylsulphamide | |
| KR101069226B1 (ko) | 3,4-디클로로-ｎ-(2-시아노페닐)-5-이소티아졸카복사미드의 제조방법 | |
| SU753360A3 (ru) | Способ получени 6,7-диметокси-4амино-2(4,/2-фуроил/-1-пиперазинил)хиназолина | |
| KR101170192B1 (ko) | 1,2-벤즈이속사졸-3-메탄술폰아미드의 원-포트 제조방법 | |
| CA1102332A (en) | Intermediate product for the production of 6,7- dimethoxy-4-amino-2-¬4-(2-furoyl)-1- piperazinyl|quinazoline having an antihypertensive effect | |
| US3937703A (en) | Preparation of rdx | |
| EP0325183A2 (en) | Method for the production of 2-oxyimino-3-oxobutyric acids | |
| CA1110385A (en) | Polymeric activated esters of 3,4-di-hydroxy-2,5- diphenyl-thiophene-1,1-di-oxide | |
| KR20000018793A (ko) | 1,2-벤즈이소티아졸린-3-온의 제조방법 | |
| SU516688A1 (ru) | Способ получени производных 1,2,4-дитиазепина | |
| JPS6053021B2 (ja) | ヒダントインの製造法 | |
| KR940000239B1 (ko) | 2-메틸-4-이소티아졸린-3-온 염의 제조방법 | |
| JPH0331252A (ja) | スルフェニルオキシムカーバメート誘導体の製造方法 | |
| JPH0368571A (ja) | Ｎ―置換２、４、６―トリイミノトリアジン誘導体の製造方法 | |
| JPH0782242A (ja) | Ｎ−置換−１−メチルチオ−２−ニトロエテンアミン類の単離方法 |