SE424993B - INTERMEDIATE FOR THE PREPARATION OF 6,7-DIMETOXY-4-AMINO-2- / 4- (2-FUROYL) -1-PIPERAZINYL / CHINAZOLINE WITH ANTI-BLOOD PRESSURE EFFECT - Google Patents
INTERMEDIATE FOR THE PREPARATION OF 6,7-DIMETOXY-4-AMINO-2- / 4- (2-FUROYL) -1-PIPERAZINYL / CHINAZOLINE WITH ANTI-BLOOD PRESSURE EFFECTInfo
- Publication number
- SE424993B SE424993B SE7713377A SE7713377A SE424993B SE 424993 B SE424993 B SE 424993B SE 7713377 A SE7713377 A SE 7713377A SE 7713377 A SE7713377 A SE 7713377A SE 424993 B SE424993 B SE 424993B
- Authority
- SE
- Sweden
- Prior art keywords
- furoyl
- dimethoxy
- piperazinyl
- amino
- preparation
- Prior art date
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
7713377-5 till åtskillnzmd från kända förfaranden, bildandet av kinazolinríngen sker inne i molekylen till den slutliga produkten. Mellanprodukten enligt uppfinningen är 3,4-dimetoxi-6-¿í-(2Åfuroyl)-l-piperazinyltio- karbamidgfbenzonitril med formeln c H - c N 0 H3o\ H N _ oc II \L__/ \ I 5 .__ CHBO/ cN Framställning av prazosin (I) med utgång från mellanprodukten enligt uppfinningen kan utföras sålunda, att 3,4-dimetoxi-6-¿ï-(2-furoyl)-1- piperazinyltiokarbamidgfbenzonitril bringas att reagera med metyl- jodid för bildande av metyl-N-(3,4-dimetoxi-6-cyanofenyl)-¿Ã-(2- furoyl)-1-piperazinyl7tioformamidat med formeln CHQ\ /N=C-N y-OC_/O 3 @ ' |SCH\__ \\ f III 3 cH3o/ \cN och denna förening cykliseras genom upphettning av densamma tillsam- mans med ammoniak i ett polärt lösningsmedel under närvaro av alkali-å metallamid. 7713377-5 to distinguish from known methods, the formation of the quinazoline ring takes place inside the molecule of the final product. The intermediate of the invention is 3,4-dimethoxy-6-β- (2-furoyl) -1-piperazinylthio-urea-benzonitrile of the formula c H - c N 0 H 30 \ HN - and II \ L __ / \ I 5 .__ CHBO / cN Preparation of prazosin (I) starting from the intermediate of the invention can be carried out in such a way that 3,4-dimethoxy-6-β- (2-furoyl) -1-piperazinylthioureagbenzonitrile is reacted with methyl iodide to form methyl-N- (3,4-dimethoxy-6-cyanophenyl) -β- (2-furoyl) -1-piperazinyl] thioformamide of the formula CHQ \ / N = CN y-OC_ / O 3 @ '| SCH \ __ \\ f III 3 cH3o and this compound is cyclized by heating it together with ammonia in a polar solvent in the presence of alkali metal amide.
Med utgång från mellanprodukten II enligt uppfinningen är det möjligt att utföra framställningen av prazosin kontinuerligt i ett och samma lösningsmedel utan avskiljande av mellanprodukter, vilket gör fram- ställningen synnerligen enkel.Starting from the intermediate II according to the invention, it is possible to carry out the preparation of prazosin continuously in one and the same solvent without separation of intermediates, which makes the preparation extremely simple.
Mellanprodukten II enligt uppfinningen kan framställas genom att 3,4-dimetoxi-6-aminobenzonitril med formeln NH CH 30 2 IV CH3O CN brinqas att ruagera med tiofosgen för bildande av 3,4-dimetoxi-6-iso- tiocyanatobenzonitril med formeln cn3o\Û/Ncs v / \/: \ CN CH3O 7713377-5 och denna förening bringas att reagera med l-(2-furoyl)piperazin med formeln /“"\ :m N - oc-fo? \_/ L VI eller l-(2-furoyl)piperazin enligt formeln VI bringas att reagera med tio- fosgen för bildande av 4-(2-furoyl)piperazinyltiokarbonylklorid med formeln / \ cl-c-N N -oc../ W VII g \___/ L och denna förening bringas att reagera med 3,4-dimetoxi-6-aminobenzo- nitril enligt formeln IV.The intermediate II of the invention can be prepared by reacting 3,4-dimethoxy-6-aminobenzonitrile of the formula NH CH 3 2 CH 3 O CH 3 CN with the formation of thiophosgene to give 3,4-dimethoxy-6-isothiocyanatobenzonitrile of the formula cn 3 O CNC 3 7713377-5 and this compound is reacted with 1- (2-furoyl) piperazine of the formula N (2-furoyl) piperazine of formula VI is reacted with thiophosgene to form 4- (2-furoyl) piperazinylthiocarbonyl chloride of the formula / \ cl-cN N -oc ../ W VII g \ ___ / L and this compound reacted with 3,4-dimethoxy-6-aminobenzonitrile of formula IV.
För åskådliggörande av uppfinningen anföres följande exempel.To illustrate the invention, the following examples are given.
Exempel l a) 3,4-dimetox1-6-isotiocyanatobenzonitril (V) 27,0 g (0,l5 mol) 3,4~dimetoxi-6-aminobenzonitril (IV) upplöses i 150 ml 1,2-dikloretan och tillsättes småningom vid 0-SOC i en bland- ning av 23,0 g (0,2 mol) tiofosgen, 100 ml 1,2-dikloretan, 20,0 g (0,2 mol) kalciumkarbonat samt 200 ml vatten. Efter tillsatsen ut- föres omblandning ännu under l timme vid 0~5°C, därefter 16 timmar vid 20°C och slutligen l timme vid 3500. Reaktionsblandninqen filtre- ras och dikloretanskiktet separeras, tvättas med utspädd klorväte- syra samt vatten och torkas md MgSO4. Lösningsmedlet avlägsnas i vakuum och den kristallina resten (sp. 126-l27oC) användes såsom sådan för följande steg. Man erhåller 31,0 g (94 % av det teoretiska) 3,4-dimetoxi~6-isotiocyanatobenzonitril.Example 1a) 3,4-Dimethoxy-1-6-isothiocyanatobenzonitrile (V) 27.0 g (0.15 mol) of 3,4-dimethoxy-6-aminobenzonitrile (IV) are dissolved in 150 ml of 1,2-dichloroethane and gradually added at O-SOC in a mixture of 23.0 g (0.2 mol) of thiophosgene, 100 ml of 1,2-dichloroethane, 20.0 g (0.2 mol) of calcium carbonate and 200 ml of water. After the addition, mixing is carried out for a further 1 hour at 0 ~ 5 ° C, then 16 hours at 20 ° C and finally for 1 hour at 3500. The reaction mixture is filtered and the dichloroethane layer is separated, washed with dilute hydrochloric acid and water and dried. MgSO4. The solvent is removed in vacuo and the crystalline residue (m.p. 126-127 ° C) is used as such for the following steps. 31.0 g (94% of theory) of 3,4-dimethoxy-6-isothiocyanatobenzonitrile are obtained.
Cl0H8N2O2S Beräknat C = 54,53 Iakttaget C = 53,43 H = 3,66 H = 3,78 N = 12,72 N = 12,18 S = l4,56 S = 13,79 b) 3,4'åimGt0Xi-6-ÅÃ-(2~fur0yl)-1-piperazinyltiokarbamid97~ benzonitril (II) ll,2 g (0,05l mol) 3,4-dimetoxi-6-isotiocyanatobenzonitril (V) upplöses i 65 ml etylacetat och tillsättes under omblandninq vid OOC 7713577-5 småningom i en lösning med 9,2 g (0,05l mol) l-(2-furoyl)-piperazin i 65 ml etylacetat. Lösningen får stå över natten i -25°C, varvid produkten kristalliseras. Filtrering utföres och kristallerna tvät- tas med kallt etylacetat samt torkas. Erhålles 16,3 g (80 % av det teoretiska) 3,4-dimetoxi-6-¿É-(2-furoyl)-l-piperazinyltiokarbamidg7- benzonitrii. sp. 17s-1ao°c.Cl0H8N2O2S Calculated C = 54.53 Observed C = 53.43 H = 3.66 H = 3.78 N = 12.72 N = 12.18 S = 14.56 S = 13.79 b) 3.4'aimGt0Xi -6-α- (2-furoyl) -1-piperazinylthiourea97-benzonitrile (II) 11.2 g (0.05l mol) 3,4-dimethoxy-6-isothiocyanatobenzonitrile (V) are dissolved in 65 ml of ethyl acetate and added with mixing at 0 ° C 7713577-5 eventually in a solution of 9.2 g (0.05l mol) of 1- (2-furoyl) -piperazine in 65 ml of ethyl acetate. The solution is allowed to stand overnight at -25 ° C, whereby the product crystallizes. Filtration is performed and the crystals are washed with cold ethyl acetate and dried. 16.3 g (80% of theory) of 3,4-dimethoxy-6-N- (2-furoyl) -1-piperazinylthiourea and benzonitrile are obtained. sp. 17s -1 ° C.
C]9H20H4O4S Beräknat C = 56,99 lakttaget C = 57,41 H - 5,03 H - 5,39 N = 13,99 N = 14,14 S = 8,01 S = 7,68 Exïflæll 3,4-dimetoxi-6-¿ï-(2-furoyl)-l-piperazinyltiokarbamidgf-benzonitril (II) ' 5,0 g (0,028 ml) l-{2-furoyl)-piperazin (VI) och 2,83 g (0,028 mol) trietylamin upplöses i 60 ml diklormetan. Denna lösning tillsättes under omblandning vid ca 0°C i en blandning med 3,86 g (0,0336 mol) tiofosgen i 50 ml diklormetan. Efter tillsatsen utföres omblandning i 2 timmar vid 0°C och 3 timmar vid rumstemperatur. Trietylaminhydrc- kloriden avfiltreras och lösningen indunstas i vakuum. Resten, 4-(2- furoyl)-piperazinyltiokarbonylklorid (VII) upplöses på nytt i 50 ml diklormetan och tillsättes under omrörinq vid OOC i en lösning med 4,98 g (0,028 mol) 3,4-dimetoxi-6-aminobenzonitril (IV) och 2,83 g (0,028 mol) trietylamin i 60 ml diklormetan. Utföres omblandning i 2 timmar vid 0°C och därefter 2-3 timmar vid rumstemperatur. Trietyl- aminhydrokloriden avfiltreras och lösningen tvättas med vatten, tor- kas med MgSO4 och torrindunstas i vakuum. Erhâlles 6,2 g (55 % av det teoretiska) 3,4-dimetoxi-6-¿Ã-(2-furoyl)-l-piprazinyltiokarh- amidg7benzonitril. Sp. l75-l78°C.C] 9H20H4O4S Calculated C = 56.99 lactated C = 57.41 H - 5.03 H - 5.39 N = 13.99 N = 14.14 S = 8.01 S = 7.68 Exï fl æll 3,4- dimethoxy-6- [1- (2-furoyl) -1-piperazinylthiourea] -benzonitrile (II) 5.0 g (0.028 ml) 1- (2-furoyl) -piperazine (VI) and 2.83 g (0.028 mol triethylamine is dissolved in 60 ml of dichloromethane. This solution is added with mixing at about 0 ° C in a mixture of 3.86 g (0.0336 mol) of thiophosgene in 50 ml of dichloromethane. After the addition, mixing is carried out for 2 hours at 0 ° C and 3 hours at room temperature. The triethylamine hydrochloride is filtered off and the solution is evaporated in vacuo. The residue, 4- (2-furoyl) -piperazinylthiocarbonyl chloride (VII) is redissolved in 50 ml of dichloromethane and added with stirring at 0 ° C in a solution of 4.98 g (0.028 mol) of 3,4-dimethoxy-6-aminobenzonitrile (IV ) and 2.83 g (0.028 mol) of triethylamine in 60 ml of dichloromethane. Mixing is carried out for 2 hours at 0 ° C and then for 2-3 hours at room temperature. The triethylamine hydrochloride is filtered off and the solution is washed with water, dried over MgSO 4 and evaporated to dryness in vacuo. 6.2 g (55% of theory) of 3,4-dimethoxy-6-α- (2-furoyl) -1-piprazinylthiocarhamide benzonitrile are obtained. Sp. 175-78 ° C.
Framställningen av pyrazosin med utgång från mellanprodukten en~ ligt uppfinningen kan utföras på följande sätt. äxsßlnslí a) Metyl-N-(3,4-dímetoxi-6-cyanofenyl)-/Ä-(2-furoyl)-l-piperazinyl/- tioformamidat-hydrojodid (III-UI) 20,0 g (0,05 mol) 3,4-dimetoxi-6-¿Ã-(2-furoyl)-1-piprazinyltio~ karbamid§Ybenzonitril upplöses i 200 ml bis-metoxietyleter (diglym) och tillsättes 14,2 g (0,1 mel) metyljodid. Blandningen upphettas 7713377-5 tillsammans med en återloppskylare i 9 timmar vid 6000- Lößniflqen ned- kyles till rumstemperatur och filtreras. Den kristallina reaktions- produkten tvättas med eter och torkas. Erhålles 24,6 g (90 % av det teoretiska) mety1-N-(3,4-dimetoxi-6-cyanofenyl)-[Ä-(2-furoyl)-1- piperazinylYtioformamidat-hydrojodid. Sp. 16300.The preparation of pyrazosin starting from the intermediate according to the invention can be carried out in the following manner. Exylserine a) Methyl N- (3,4-dimethoxy-6-cyanophenyl) - N- (2-furoyl) -1-piperazinyl / thioformamide hydroiodide (III-UI) 20.0 g (0.05 mol ) 3,4-Dimethoxy-6-β- (2-furoyl) -1-piprazinylthiourea} benzonitrile is dissolved in 200 ml of bis-methoxyethyl ether (diglyme) and 14.2 g (0.1 ml) of methyl iodide are added. The mixture is heated together with a reflux condenser for 9 hours at 6000 ° C. The mixture is cooled to room temperature and filtered. The crystalline reaction product is washed with ether and dried. 24.6 g (90% of theory) of methyl N- (3,4-dimethoxy-6-cyanophenyl) - [α- (2-furoyl) -1-piperazinyl] thioformamide hydroiodide are obtained. Sp. 16300.
C20H23IN4O4S Beräknat C = 44,29 Iakttaqet C = 44,25 H = 4,27 H = 4,26 I = 23,39 I = 22,93 = 10,33 = 9,61 S ~ 5,91 S = 5,58 b) Metyl-N-(3,4-dimetoxi-6-cyanofenyl)-¿4~(2-furoyl)-l-piperazi- nyl/tioformamidat (III) 62,0 g (0,ll4 mol) metyl-N-(3,4-dimetoxi-6-cyanofenyl)-/4-(2~furoy1)- 1-piperazinyl/tioformamidat-hydrojodid upplöses vid 0-SOC i 350 ml metanol och under omröring tillsättes 186 ml 25 % ammoniaklösninq.C20H23IN4O4S Calculated C = 44.29 Observation C = 44.25 H = 4.27 H = 4.26 I = 23.39 I = 22.93 = 10.33 = 9.61 S ~ 5.91 S = 5, 58 b) Methyl-N- (3,4-dimethoxy-6-cyanophenyl) -4- (2-furoyl) -1-piperazinyl / thioformamide (III) 62.0 g (0.114 mol) of methyl- N- (3,4-Dimethoxy-6-cyanophenyl) - [4- (2-furoyl) -1-piperazinyl] thioformamide hydroiodide is dissolved at 0 ° C in 350 ml of methanol and 186 ml of 25% ammonia solution are added with stirring.
Omröring utföres under 2 timmar i OOC, produkten filtreras och tvät- tas med eter. Erhålles 42,7 g (90 % av det teoretiska) metyl-N-(3,4- dimetoxi-6~cyanofenyl)-¿4-(2-furoyl)-1-piperazinyl7tiofonmamidat. sp. 1o5-1o7°c.Stirring is carried out for 2 hours in 0 ° C, the product is filtered and washed with ether. 42.7 g (90% of theory) of methyl N- (3,4-dimethoxy-6-cyanophenyl) -4- (2-furoyl) -1-piperazinyl] thiophonamidate are obtained. sp. 1o5-1o7 ° c.
C20H22N404S Beräknat C = 57,95 Itakttaqet C = 58,01 H = 5,36 H = 5,54 N = 13,52 N = 13,73 S = 7,73 S = 7,53 c) 6,7-dimetoxi-4-amino-2-/4-(2-furoyl)-l-piperazinyl/- kinazolin (I) 7,0 g (0,0l7 mel) metyl-N~(3,4-dimetoxi-6-cyanofenyl)-/4~(2~furoyl)- lfiüperazinyl/tioformamidat upplöses i 100 ml formamid och tillsättes 2,0 q (0,05l mol) natriumamid. Lösningen mättas med NH3-gas vid OOC.C20H22N4O4S Calculated C = 57.95 Rate of action C = 58.01 H = 5.36 H = 5.54 N = 13.52 N = 13.73 S = 7.73 S = 7.53 c) 6,7-dimethoxy -4-amino-2- [4- (2-furoyl) -1-piperazinyl] quinazoline (I) 7.0 g (0.017 ml) methyl-N- (3,4-dimethoxy-6-cyanophenyl) - [4 - (2-furoyl) - 1-hyperazinyl / thioformamide is dissolved in 100 ml of formamide and 2.0 g (0.05l mol) of sodium amide are added. The solution is saturated with NH 3 gas at 0 ° C.
Lösningens temperatur höjes långsamt till l200C och lösningen upp- hettas under 24 timmar i denna temperatur under samtidig tillförsel av NH3-gas. Den avkylaa reaktionsblandningen hälles i 100 ml isvatten och extraheras 6-7 gånger med 50 ml kloroform. Kloroformaextraktet tvättas 4 qånqvr med 50 ml vatten, torkas och torrindunstas i vakuum.The temperature of the solution is slowly raised to 120 DEG C. and the solution is heated for 24 hours at this temperature while simultaneously supplying NH3 gas. The cooled reaction mixture is poured into 100 ml of ice water and extracted 6-7 times with 50 ml of chloroform. The chloroform extract is washed 4 times with 50 ml of water, dried and evaporated to dryness in vacuo.
Produkten krístalliseras från etanol-vatten-blandningen (50:15).The product crystallizes from the ethanol-water mixture (50:15).
Hrhålles 6,7-dimetoxl-4-aminu~2-¿4-(2-furoyl)-l-piprazinyl/kinazo- lin. Sp. 262-264°C. Produktens IR- och NMR-spektra är identiska 7713377-5 med spektra för den förening som framställes enliqt tidigare inom litteraturen anvisade förfaranden.6,7-Dimethoxy-4-amino-2- [4- (2-furoyl) -1-piprazinyl] quinazoline is retained. Sp. 262-264 ° C. The IR and NMR spectra of the product are identical to the spectra of the compound prepared according to methods previously described in the literature.
Cl9H2lN5O4 Beräknat C = 59,52 Iakttaget C = 59,28 H = 5,52 H = 5,88 N = 18,27 N = 17,99 Exemgel 4 6,7-dimetoxi-4-amino-2-¿ï-(2-furoyl)-l-piperazinyl7-kinazolin (I) 17,6 g (0,044 mol) 3,4-dimetoxi-6-¿ï-(2-furoyl)-l-piperazinyltio- Innbæmdg7Fbenzonitril upplöses i 100 ml formamid och tillsättes 12,5 g (0,088 mol) metyljodid och upphettas i 9 timmar vid 60°C. överloppsmängden metyljodid brinqas att avdunsta och lösningen mättas med NH3-gas i OOC och till lösningen adderas 6,9 g (0,176 mol) nat- riumamid. Temperaturen höjes till l2O-14000 och upphettning sker i 24 timmar i denna temperatur under samtidig tillförsel av en NH3- gas. Den avkylda reaktionsblandningen hälles i isvatten (ca 150 ml) och extraheras med kloroform (8 x 50 ml). Kloroformextraktet tvät- tas med vatten, behandlas med aktivkol, torkas och torrindunstas i vakuum. Resten kristalliseras ur etanol-vatten-blandningen (50:15).C 19 H 21 N 5 O 4 Calculated C = 59.52 Observed C = 59.28 H = 5.52 H = 5.88 N = 18.27 N = 17.99 Example 4 6,7-dimethoxy-4-amino-2-β (2-Furoyl) -1-piperazinyl-7-quinazoline (I) 17.6 g (0.044 mol) of 3,4-dimethoxy-6-β- (2-furoyl) -1-piperazinylthio- 12.5 g (0.088 mol) of methyl iodide are added and heated for 9 hours at 60 ° C. the excess amount of methyl iodide is forced to evaporate and the solution is saturated with NH 3 gas in 0 ° C and 6.9 g (0.176 mol) of sodium amide are added to the solution. The temperature is raised to 120-14000 and heating takes place for 24 hours at this temperature while simultaneously supplying an NH3 gas. The cooled reaction mixture is poured into ice water (about 150 ml) and extracted with chloroform (8 x 50 ml). The chloroform extract is washed with water, treated with activated carbon, dried and evaporated to dryness in vacuo. The residue is crystallized from the ethanol-water mixture (50:15).
Erhâlles 6,7-dimetoxi-4-amino-2-[Ã-(2~furoyl)-l-piperazinyl7kinazo~ lin. sp. 263-2ss°c.6,7-dimethoxy-4-amino-2- [α- (2-furoyl) -1-piperazinyl] quinazoline is obtained. sp. 263-2ss ° C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI763614A FI58124C (en) | 1976-12-15 | 1976-12-15 | NY MELLANPROTUKT 3,4-DIMETOXY-6- (4- (2-FUROYL) -1-PIPERAZINYLTHOUREA) -BENONITRIL FOR FRAMSTAELLNING AV 6,7-DIMETOXY-4-AMINO-2- (4- (2-FUROYL) -1 -PIPERAZINYL) QUINAZOLINE WITH BLODTRYCKSSAENKANDE VERKAN |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7713377L SE7713377L (en) | 1978-06-16 |
| SE424993B true SE424993B (en) | 1982-08-23 |
Family
ID=8510504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7713377A SE424993B (en) | 1976-12-15 | 1977-11-25 | INTERMEDIATE FOR THE PREPARATION OF 6,7-DIMETOXY-4-AMINO-2- / 4- (2-FUROYL) -1-PIPERAZINYL / CHINAZOLINE WITH ANTI-BLOOD PRESSURE EFFECT |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS5387375A (en) |
| AT (1) | AT358047B (en) |
| BE (1) | BE861822A (en) |
| CA (1) | CA1102332A (en) |
| CH (1) | CH630624A5 (en) |
| CS (1) | CS197312B2 (en) |
| DD (1) | DD134226A1 (en) |
| DE (1) | DE2755638A1 (en) |
| DK (1) | DK145822C (en) |
| FI (1) | FI58124C (en) |
| HU (1) | HU174048B (en) |
| NL (1) | NL7713703A (en) |
| NO (1) | NO146239C (en) |
| PL (1) | PL106201B1 (en) |
| SE (1) | SE424993B (en) |
| SU (1) | SU923370A3 (en) |
| ZA (1) | ZA777222B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI67699C (en) * | 1979-01-31 | 1985-05-10 | Orion Yhtymae Oy | PROCEDURE FOR THE FRAMSTATION OF AV 6,7-DIMETOXY-4-AMINO-2- (4- (2-FUROYL) -1-PIPERAZINYL) QUINAZOLINE HYDROCHLORIDE WITH BLODTRYCKSSAENKANDE VERKAN |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
-
1976
- 1976-12-15 FI FI763614A patent/FI58124C/en not_active IP Right Cessation
-
1977
- 1977-11-24 CH CH1438277A patent/CH630624A5/en not_active IP Right Cessation
- 1977-11-25 SE SE7713377A patent/SE424993B/en not_active IP Right Cessation
- 1977-12-05 AT AT867177A patent/AT358047B/en not_active IP Right Cessation
- 1977-12-05 ZA ZA00777222A patent/ZA777222B/en unknown
- 1977-12-11 NL NL7713703A patent/NL7713703A/en not_active Application Discontinuation
- 1977-12-12 NO NO774263A patent/NO146239C/en unknown
- 1977-12-13 PL PL1977202898A patent/PL106201B1/en unknown
- 1977-12-13 HU HU77OI217A patent/HU174048B/en not_active IP Right Cessation
- 1977-12-14 BE BE183425A patent/BE861822A/en not_active IP Right Cessation
- 1977-12-14 DE DE19772755638 patent/DE2755638A1/en not_active Ceased
- 1977-12-14 CA CA293,066A patent/CA1102332A/en not_active Expired
- 1977-12-14 DK DK558377A patent/DK145822C/en not_active IP Right Cessation
- 1977-12-14 SU SU772555751A patent/SU923370A3/en active
- 1977-12-15 JP JP15157177A patent/JPS5387375A/en active Granted
- 1977-12-15 CS CS778433A patent/CS197312B2/en unknown
- 1977-12-15 DD DD77202667A patent/DD134226A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5387375A (en) | 1978-08-01 |
| DE2755638A1 (en) | 1978-06-22 |
| DD134226A1 (en) | 1979-02-14 |
| DK558377A (en) | 1978-06-16 |
| CA1102332A (en) | 1981-06-02 |
| ATA867177A (en) | 1980-01-15 |
| BE861822A (en) | 1978-03-31 |
| SU923370A3 (en) | 1982-04-23 |
| PL202898A1 (en) | 1978-08-28 |
| DK145822C (en) | 1983-08-29 |
| NO774263L (en) | 1978-06-16 |
| FI58124B (en) | 1980-08-29 |
| PL106201B1 (en) | 1979-12-31 |
| NO146239B (en) | 1982-05-18 |
| CH630624A5 (en) | 1982-06-30 |
| NL7713703A (en) | 1978-06-19 |
| ZA777222B (en) | 1978-09-27 |
| SE7713377L (en) | 1978-06-16 |
| AT358047B (en) | 1980-08-11 |
| DK145822B (en) | 1983-03-14 |
| CS197312B2 (en) | 1980-04-30 |
| FI58124C (en) | 1980-12-10 |
| NO146239C (en) | 1982-08-25 |
| HU174048B (en) | 1979-10-28 |
| JPS6225145B2 (en) | 1987-06-01 |
| FI763614A (en) | 1978-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5675006A (en) | Methods of making ureas and guanidines, including, terazosin, prazosin, doxazosin, tiodazosin, trimazosin, quinazosin, and bunazosin (exemplary of 2- substituted quinazoline compounds), and meobentine, and bethanidine and intermediates therefor | |
| FI59991B (en) | PROCEDURE FOR THE FRAMSTATION OF AV 2-ARYLAMINO-2-IMIDAZOLINE DERIVATIVES AND DERAS SALTER | |
| JPS5930713B2 (en) | Method for producing novel substituted 6-aryl-4H-S-triazolo-[3,4C]-thieno-[2,3e]-1,4-diazepines | |
| HU186975B (en) | Process for preparing new triazolo-quinazolone derivatives | |
| SE424993B (en) | INTERMEDIATE FOR THE PREPARATION OF 6,7-DIMETOXY-4-AMINO-2- / 4- (2-FUROYL) -1-PIPERAZINYL / CHINAZOLINE WITH ANTI-BLOOD PRESSURE EFFECT | |
| SE459808B (en) | CHEMICAL COMPOSITION THAT CAN BE USED AS INTERMEDIATE FOR THE PREPARATION OF 4-METHYL-5-ALKYLTYOMETHYLIMIDAZOLES | |
| Sasaki et al. | Polycyclic N‐Heterocyclic Compounds. 56 Reaction of N‐(5, 6‐Dihydro [1] benzoxepino [5, 4‐d] pyrimidin‐4‐yl) amidine or Its Amide Oxime Derivatives with Hydroxylamine Hyrdochloride | |
| SE430692B (en) | SET TO PREPARE 6,7-DIMETOXY-4-AMINO-2- (4- (2-FUROYL) -1-PIPERAZINYL) CHINAZOLINE HYDROCHLORIDE WITH ANTIHYPERTENSIVE EFFECT | |
| DK144972B (en) | METHOD FOR PREPARING 6,7-DIMETHOXY-4-AMINO-2- (4- (2-FUROYL) -1-PIPERAZINYL) QUINAZOLINE | |
| Fathy et al. | Activated nitriles in heterocyclic synthesis: a one-step synthesis of several new pyrimidine, pyridine, and pyrazole derivatives | |
| US3361745A (en) | 1-alkenyl-3-alkyl-6-amino-5-(substituted-methyleneamino)-1, 2, 3, 4-tetrahydro-2, 4-pyrimidinediones | |
| Radwan et al. | Synthesis and some reactions of new benzo [b] pyran derivatives | |
| FI85585B (en) | FOERFARANDE FOER FRAMSTAELLNING AV 4-ACETYL-ISOKINOLINON. | |
| KR880001105B1 (en) | Process for preparing 1-benzil-4-(4-(2-pyrimidinylamino)benjil)-2,3-dioxopiperajine derivatives | |
| SU797575A3 (en) | Method of preparing quinazolinone oxides | |
| HU196771B (en) | Process for production of intermediers of derivatives of oxo-oxazolidinil-benzol having antibacterial effect | |
| US3472847A (en) | Conversion of pyrazinoylcyanamides to pyrazinoylguanidines | |
| LAILA et al. | Chemistry" Faculty of Science, Cairo University, AR Egypt. | |
| HRVAT | DļļAll MAPIJTIA | |
| Kelarev et al. | Synthesis and properties of sym-triazine derivatives: 9. Synthesis of 2-amino-and 2, 4-diamino-sym-triazines containing furan fragments | |
| Muralikrishna et al. | Synthesis of ureides containing indole moiety bearing-4-oxazetidinone | |
| Bernáth et al. | Stereochemische Untersuchungen, 98. Gesättigte Heterocyclen, 100. Synthese von stereoisomeren 2-Ethylimino-3, 1-perhydrobenzoxazinen und benzothiazinen | |
| HU203333B (en) | Process for producing n-cyano-carboxamidine derivatives | |
| NO138658B (en) | ANALOGICAL PROCEDURES FOR THE PREPARATION OF NEW THERAPEUTICALLY ACTIVE PIPERIDE DERIVATIVES AND THEIR SALTS | |
| HU215850B (en) | Process for producing thiocyanatoketone derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NUG | Patent has lapsed |
Ref document number: 7713377-5 Effective date: 19900706 Format of ref document f/p: F |