NO159277B - 2,6-BIS-HALOGENACYLAMINO-BENZO (1,2-D: 5,4-D [) - BISTIAZOLE DERIVATIVES SUCH AS INTERMEDIATES FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2,6-BISAMINOBINZO- (1,2-D: 5, 4-D [) bisthiazole derivative. - Google Patents
2,6-BIS-HALOGENACYLAMINO-BENZO (1,2-D: 5,4-D [) - BISTIAZOLE DERIVATIVES SUCH AS INTERMEDIATES FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2,6-BISAMINOBINZO- (1,2-D: 5, 4-D [) bisthiazole derivative. Download PDFInfo
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- NO159277B NO159277B NO85851549A NO851549A NO159277B NO 159277 B NO159277 B NO 159277B NO 85851549 A NO85851549 A NO 85851549A NO 851549 A NO851549 A NO 851549A NO 159277 B NO159277 B NO 159277B
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- Prior art keywords
- benzo
- bisthiazole
- bis
- hydrogen
- methyl
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- 239000000543 intermediate Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- -1 NH 2 Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000005448 ethoxyethyl group Chemical class [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical class 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
- 229940116357 potassium thiocyanate Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NSTNTKKWRMLJQB-UHFFFAOYSA-N 4-chloro-8-(trifluoromethyl)-[1,3]thiazolo[4,5-f][1,3]benzothiazole-2,6-diamine Chemical compound FC(F)(F)C1=C2SC(N)=NC2=C(Cl)C2=C1SC(N)=N2 NSTNTKKWRMLJQB-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 1
- DYFFUJNIXCDLOR-UHFFFAOYSA-N (4-nitrophenyl) 2-chloroacetate Chemical compound [O-][N+](=O)C1=CC=C(OC(=O)CCl)C=C1 DYFFUJNIXCDLOR-UHFFFAOYSA-N 0.000 description 1
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 1
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
- HSOWWQNFYIFDRG-UHFFFAOYSA-N 2,6-diamino-4-chloro-[1,3]thiazolo[4,5-f][1,3]benzothiazole-8-carbonitrile Chemical compound N#CC1=C2SC(N)=NC2=C(Cl)C2=C1SC(N)=N2 HSOWWQNFYIFDRG-UHFFFAOYSA-N 0.000 description 1
- YCWXOQCYLKOSKL-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)benzene-1,3-diamine Chemical compound NC1=CC(C(F)(F)F)=CC(N)=C1Cl YCWXOQCYLKOSKL-UHFFFAOYSA-N 0.000 description 1
- AJYCIEHSLYUBEI-UHFFFAOYSA-N 3,5-diamino-4-chlorobenzonitrile Chemical compound NC1=CC(C#N)=CC(N)=C1Cl AJYCIEHSLYUBEI-UHFFFAOYSA-N 0.000 description 1
- ALSFHDCCAKIYIQ-UHFFFAOYSA-N [1,3]thiazolo[4,5-f][1,3]benzothiazole-2,6-diamine Chemical compound C1=C2SC(N)=NC2=CC2=C1SC(N)=N2 ALSFHDCCAKIYIQ-UHFFFAOYSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940018564 m-phenylenediamine Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
Denne oppfinnelse angår nye forbindelser som er egnet This invention relates to new compounds which are suitable
som mellomprodukter for syntese av 2,6-bisaminobenzo-f1,2-d: 5,4-d']-bis-tiazoler som har antiartritiske og antirevmatiske egenskaper, og som har den generelle formel as intermediates for the synthesis of 2,6-bisaminobenzo-f1,2-d:5,4-d']-bis-thiazoles which have antiarthritic and antirheumatic properties, and which have the general formula
hvor where
R^ er hydrogen, metyl eller etyl; R 1 is hydrogen, methyl or ethyl;
R2 er gruppen R2 is the group
R3 og R4, som er like eller forskjellige, er hydrogen, Cl, Br, NH2, N02, CH3, OCH3, CN, CF3, COOC2H5 eller C6H5; R 3 and R 4 , which are the same or different, are hydrogen, Cl, Br, NH 2 , NO 2 , CH 3 , OCH 3 , CN, CF 3 , COOC 2 H 5 or C 6 H 5 ;
R5 er hydrogen, C1-C3-alkyl, eventuelt metyl subst i tuert C3-Cg-cykloalkyl, fenyl, etoksyetyl; R5 is hydrogen, C1-C3-alkyl, optionally methyl substituted C3-C8-cycloalkyl, phenyl, ethoxyethyl;
R5 er hydrogen, C1-C3-alkyl, etoksyetyl, eller R 5 is hydrogen, C 1 -C 3 alkyl, ethoxyethyl, or
R5 og R(j sammen med ni trogenatomet, som de er bundet til, betyr en tiazol-, morfolin-, eller tiamorfollnr ing; en eventuelt med en hydroksymetyl-, hydroksyetyl-, benzyl- eller piperidin-l-yl-gruppe substituert piperidinring; en N-metyl-, N-benzyl-, K-trifluoretyl-, N-fenyl-, N-fluorfenyl-, N-klorfenyl-, N-acetylfenyl-, N-trifluormetylfenyl-, N-piperidylfenyl-, N-hydroksyetyl-, N-etoksykarbonyl- eller N-etoksykarbonylmetyl-substituert piperazin-l-yl-rest; eller 2,5-dimetylpiperazinyl-rest, og R5 and R(j together with the nitrogen atom to which they are attached mean a thiazole, morpholine or thiamorphol ring; a piperidine ring optionally substituted with a hydroxymethyl, hydroxyethyl, benzyl or piperidin-1-yl group ; a N-methyl-, N-benzyl-, K-trifluoroethyl-, N-phenyl-, N-fluorophenyl-, N-chlorophenyl-, N-acetylphenyl-, N-trifluoromethylphenyl-, N-piperidylphenyl-, N-hydroxyethyl -, N-ethoxycarbonyl- or N-ethoxycarbonylmethyl-substituted piperazin-1-yl residue; or 2,5-dimethylpiperazinyl residue, and
A er C1-C2 -alkylenrest. A is C1-C2 -alkylene residue.
I henhold til oppfinnelsen tilveiebringes 2,6-bis-halogenacyl-amino-benzo-ti,2-d:5,4-d<*>]-bistiazol-derivater med den generelle formel According to the invention, 2,6-bis-halogenacyl-amino-benzo-thi,2-d:5,4-d<*>]-bisthiazole derivatives with the general formula are provided
hvor R^, R3, R4 og A har de ovenfor angitte betydninger, og Hal betyr et halogenatom, og syreaddisjonssalter derav. Forbindelsene med den generelle formel I kan fremstilles ved at en 2,6-diaminobenzo-bistiazol med formel IV where R 1 , R 3 , R 4 and A have the meanings given above, and Hal means a halogen atom, and acid addition salts thereof. The compounds of the general formula I can be prepared by a 2,6-diaminobenzobisthiazole of the formula IV
hvor R^, R3 og R^ er som ovenfor angitt, omsettes med et halogen-acylhalogenid eller -anhydrid eller med et p-nitrofenyl-halogen-karboksylat. Omsetningen foretas hensiktsmessig i nærvær av et oppløsningsmiddel så som dimetylformamid eller dioksan. where R 1 , R 3 and R 2 are as indicated above, is reacted with a halogen acyl halide or anhydride or with a p-nitrophenyl halogen carboxylate. The reaction is conveniently carried out in the presence of a solvent such as dimethylformamide or dioxane.
Under tilsetningen av halogenacylhalogenidet holdes temperaturen vanligvis lav, f.eks. mellom ca. 0 og +10°C. Ved slutten av tilsetningen får temperaturen vanligvis stige opp til reaksjonsblandingens kokepunkt. During the addition of the halogen acyl halide, the temperature is usually kept low, e.g. between approx. 0 and +10°C. At the end of the addition, the temperature is usually allowed to rise to the boiling point of the reaction mixture.
2,6-diaminobenzo-[1,2-d:5,4-d']-bistiazolene med formel II som anvendes som utgangsforbindelser, kan f.eks. oppnås The 2,6-diaminobenzo-[1,2-d:5,4-d']-bisthiazoles of formula II which are used as starting compounds, can e.g. is achieved
ved at et m-fenylendiamin omsettes med kaliumtiocyanat i eddiksyre som beskrevet i tysk offentliggjørelsesskrift 2 025 896. in that an m-phenylenediamine is reacted with potassium thiocyanate in acetic acid as described in German publication 2 025 896.
Anvendelse av forbindelsene med formel I for fremstilling av terapeutisk aktive forbindelser er beskrevet i stamansøkningen 78. 2734 (patent 153 851) . Use of the compounds of formula I for the production of therapeutically active compounds is described in parent application 78.2734 (patent 153 851).
De følgende eksempler tjener til å illustrere frem-stillingen av forbindelsen ifølge oppfinnelsen. The following examples serve to illustrate the preparation of the compound according to the invention.
Eksempel 1 Example 1
2, 6- bis-( kloracetylamino)- benzo-[ 1, 2- d:5, 4- d']- bistiazol. 2,6-bis-(chloroacetylamino)-benzo-[1,2-d:5,4-d']-bisthiazole.
a) Til en suspensjon av .15 g 2,6-diamino-benzo-[1,2-d:5,4-d<1>]-bistiazol i 130 ml dimetylformamid setter man ved 10°C a) A suspension of .15 g of 2,6-diamino-benzo-[1,2-d:5,4-d<1>]-bisthiazole in 130 ml of dimethylformamide is placed at 10°C
under sterk omrøring 20 ml kloracetylklorid. Derefter oppvarmer man blandingen i en time på vannbad, avkjøler den og filtrerer den, vasker med benzen og tørrer. Man får 24 g 2,6-di-(kloracetylamino)-benzo-[1,2-d:5,4-d']-bistiazol med sm.p. 330°C (fra dimetylformamid). with vigorous stirring, 20 ml of chloroacetyl chloride. The mixture is then heated for one hour on a water bath, cooled and filtered, washed with benzene and dried. 24 g of 2,6-di-(chloroacetylamino)-benzo-[1,2-d:5,4-d']-bisthiazole with m.p. 330°C (from dimethylformamide).
b) En blanding av 222 mg 2,6-diaminobenzo-[1,2-d:5,4-d']-bistiazol og 500 mg kloreddiksyre-p-nitrofenylester i 5 b) A mixture of 222 mg of 2,6-diaminobenzo-[1,2-d:5,4-d']-bisthiazole and 500 mg of chloroacetic acid p-nitrophenyl ester in 5
ml dioksan oppvarmes i 15 minutter under tilbakeløpskjøling. Den avkjølte blanding filtreres, og de utskilte krystaller vaskes og tørres. Man får 350 mg (93% av det teoretiske) 2,6-di-(kloracetylamino)-benzo-[l,2-d:5,4-d<1>]-bistiazol med sm.p. 330°C. ml of dioxane is heated for 15 minutes under reflux. The cooled mixture is filtered, and the separated crystals are washed and dried. 350 mg (93% of the theoretical) of 2,6-di-(chloroacetylamino)-benzo-[1,2-d:5,4-d<1>]-bisthiazole with m.p. 330°C.
c) 222 mg 2,6-diamino-[1,2-d:5,4-d']-bistiazol og 513 mg klor-eddiksyreanhydrid oppvarmes i 2 ml tørr dimetylformamid c) 222 mg of 2,6-diamino-[1,2-d:5,4-d']-bisthiazole and 513 mg of chloroacetic anhydride are heated in 2 ml of dry dimethylformamide
i 10 minutter under tilbakeløpskjøling. Den erholdte suspensjon tilsettes etanol, og de utskilte krystaller fra-filteres, vaskes og tørres. Man får 300 mg = 80% av det teoretiske, 2,6-di-(kloracetylamino)-benzo-[1,2-d:5,4-d']-bistiazol med sm.p. 330°C. for 10 minutes under reflux. Ethanol is added to the resulting suspension, and the separated crystals are filtered off, washed and dried. You get 300 mg = 80% of the theoretical, 2,6-di-(chloroacetylamino)-benzo-[1,2-d:5,4-d']-bisthiazole with m.p. 330°C.
Eksempel 2 Example 2
2, 6- bis- fN'- metyl- N'- kloracetyl- amino] benzo-[ 1, 2- d:5, 4- d']- bistiazol. 2, 6- bis-fN'- methyl- N'- chloroacetyl- amino] benzo-[ 1, 2- d:5, 4- d']- bisthiazole.
Til en omrørt, isavkjølt suspensjon av 6,5 g 2,6-bis-(dimetylamino)-benzo-[1,2-d:5,4-d']-bistiazol i 50 ml dimetylformamid settes 8 ml kloracetylklorid. Blandingen oppvarmes i 1,5 timer til 90°C og helles derefter i vann. Bunnfallet frafiltreres, vaskes og tørres. Man får 10 g (95% av det teoretiske) 2,6-bis-[N'-metyl-N'-kloracetyl-amino]-benzo-[1,2-d:5,4-d<1>]-bistiazol med sm.p. 250°C (spaltning, To a stirred, ice-cooled suspension of 6.5 g of 2,6-bis-(dimethylamino)-benzo-[1,2-d:5,4-d']-bisthiazole in 50 ml of dimethylformamide is added 8 ml of chloroacetyl chloride. The mixture is heated for 1.5 hours to 90°C and then poured into water. The precipitate is filtered off, washed and dried. 10 g (95% of the theoretical) of 2,6-bis-[N'-methyl-N'-chloroacetyl-amino]-benzo-[1,2-d:5,4-d<1>]- bistiazole with m.p. 250°C (decomposition,
fra dimetylformamid). from dimethylformamide).
Eksempel 3 2 , 6- bis-( kloracetylamino) - 4- klor- 8- tr i f luormetyl- benzo-[ 1, 2- d:5, 4- d']- bistiazol. Example 3 2,6-bis-(chloroacetylamino)-4-chloro-8-trifluoromethyl-benzo-[1,2-d:5,4-d']-bisthiazole.
Til en godt omrørt blanding av 6 g 2,6-diamino-4-klor-8-trifluormetyl-benzo[1,2-d:5,4-d']-bistiazol i 100 ml dimetylformamid setter man under avkjøling 10 ml kloracetylklorid. Derefter oppvarmes blandingen i en time til 60°C og får stå natten over. Bunnfallet omkrystalliseres fra dimetylformamid. Utbytte: 8,5 g = 96% av det teoretiske med sm.p. 350°C. To a well-stirred mixture of 6 g of 2,6-diamino-4-chloro-8-trifluoromethyl-benzo[1,2-d:5,4-d']-bisthiazole in 100 ml of dimethylformamide, 10 ml of chloroacetyl chloride are added while cooling . The mixture is then heated for one hour to 60°C and allowed to stand overnight. The precipitate is recrystallized from dimethylformamide. Yield: 8.5 g = 96% of the theoretical with m.p. 350°C.
Forbindelsen 2,6-diamino-4-klor-8-trifluormetyl-benzo-[1,2-d:5,4-d']-bistiazol med sm.p. 340°C får man ved omsetning av en avkjølt blanding av 2-klor-5-trifluormetyl-m-fenylendiamin (se tysk offentliggjørelsesskrift 2 025 896) og kaliumtiocyanat i eddiksyre og metanol med en oppløsning av brom i eddiksyre. The compound 2,6-diamino-4-chloro-8-trifluoromethyl-benzo-[1,2-d:5,4-d']-bisthiazole with m.p. 340°C is obtained by reacting a cooled mixture of 2-chloro-5-trifluoromethyl-m-phenylenediamine (see German publication 2 025 896) and potassium thiocyanate in acetic acid and methanol with a solution of bromine in acetic acid.
Eksempel 4 Example 4
2, 6- bis-( kloracetylamino)- 4- klor- 8- cyano- benzo-[ 1, 2-d:5, 4- d']- bistiazol. 2,6-bis-(chloroacetylamino)-4-chloro-8-cyano-benzo-[1,2-d:5,4-d']-bisthiazole.
Til en omrørt suspensjon av 2,6 g 2,6-diamin-4-klor-8-cyano-benzo-[1,2-d:5,4-d']-bistiazol i 30 ml dimetylformamid setter man ved 10°C 4 ml kloracetylklorid. Blandingen oppvarmes i 4 timer til 80°C og avkjøles, og bunnfallet omkrystalliseres fra dimetylformamid. Det erholdte 2,6-bis-(kloracetylamino)-4-klor-8-cyano-benzo-[1,2-d:5,4-d']-bistiazol smelter ved 330°C; Utbytte: 2,3 g = 58% av det teoretiske. To a stirred suspension of 2.6 g of 2,6-diamine-4-chloro-8-cyano-benzo-[1,2-d:5,4-d']-bisthiazole in 30 ml of dimethylformamide is placed at 10° C 4 ml of chloroacetyl chloride. The mixture is heated for 4 hours to 80°C and cooled, and the precipitate is recrystallized from dimethylformamide. The obtained 2,6-bis-(chloroacetylamino)-4-chloro-8-cyano-benzo-[1,2-d:5,4-d']-bisthiazole melts at 330°C; Yield: 2.3 g = 58% of the theoretical.
Forbindelsen 2,6-diamino-4-klor-8-cyano-benzo-[1,2-d:5,4-d']-bistiazol med sm.p. 350°C får man ved omsetning av 2-klor-5-cyano-m-fenylen-diamin (se tysk offentliggjørelses-skrift 2 025 896) og kaliumtiocyanat i eddiksyre og metanol med en oppløsning av brom i eddiksyre. The compound 2,6-diamino-4-chloro-8-cyano-benzo-[1,2-d:5,4-d']-bisthiazole with m.p. 350°C is obtained by reacting 2-chloro-5-cyano-m-phenylene-diamine (see German publication 2 025 896) and potassium thiocyanate in acetic acid and methanol with a solution of bromine in acetic acid.
Eksempel 5 Example 5
2, 6- bis-( kloracetylamino)- 4- metyl- benzo-[ l, 2- d:5, 4- d']-bistiazol. 2,6-bis-(chloroacetylamino)-4-methyl-benzo-[1,2-d:5,4-d']-bisthiazole.
En oppløsning av 6 g 2,6-diamino-4-metyl-benzo-[1,2-d:5,4-d']-bistiazol i 50 ml dimetylformamid behandler man ved 5°C med 10 ml kloracetylklorid. Blandingen oppvarmer man i 2 timer i vannbad. Ved avkjøling utkrystalliserer 2,6-diklor-acetylamino-4-metyl-benzo-[1,2-d:5,4-d']-bistiazol. Det vaskes og omkrystalliseres fra dimetylformamid. A solution of 6 g of 2,6-diamino-4-methyl-benzo-[1,2-d:5,4-d']-bisthiazole in 50 ml of dimethylformamide is treated at 5°C with 10 ml of chloroacetyl chloride. The mixture is heated for 2 hours in a water bath. On cooling, 2,6-dichloro-acetylamino-4-methyl-benzo-[1,2-d:5,4-d']-bisthiazole crystallizes out. It is washed and recrystallized from dimethylformamide.
Utbytte: 6,5 g = 66% av det teoretiske, sm.p. 330 C. Yield: 6.5 g = 66% of the theoretical, m.p. 330 C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO851549A NO159277C (en) | 1977-08-13 | 1985-04-18 | 2,6-BIS-HALOGENACYLAMINO-BENZO (1,2-D: 5,4-D [) - BISTIAZOLE DERIVATIVES SUCH AS INTERMEDIATES FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2,6-BISAMINOBINZO- (1,2-D: 5, 4-D [) bisthiazole derivative. |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772736652 DE2736652A1 (en) | 1977-08-13 | 1977-08-13 | 2,6-BIS- (AMINOCYLAMINO) -BENZO- ANGLE CLAMP ON 1,2-D TO 5,4-D 'ANGLE CLAMP ON -BISTHIAZOLE AND 2-AMINO-6- (AMINOACYLAMINO) -BENZO- ANGLE CLAMP ON 1, 2-D TO 5,4-D 'SQUARE BRACKET TO -BISTHIAZOLE, METHOD FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS |
| NO782734A NO153851C (en) | 1977-08-13 | 1978-08-11 | PREPARATION OF THERAPEUTIC ACTIVE 2,6-BIS- (AMINOACYLAMINO) -BENZO- (1,2-D: 5,4-D [) - BISTIAZOLES. |
| NO851549A NO159277C (en) | 1977-08-13 | 1985-04-18 | 2,6-BIS-HALOGENACYLAMINO-BENZO (1,2-D: 5,4-D [) - BISTIAZOLE DERIVATIVES SUCH AS INTERMEDIATES FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2,6-BISAMINOBINZO- (1,2-D: 5, 4-D [) bisthiazole derivative. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO851549L NO851549L (en) | 1979-02-14 |
| NO159277B true NO159277B (en) | 1988-09-05 |
| NO159277C NO159277C (en) | 1988-12-14 |
Family
ID=27187275
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO851549A NO159277C (en) | 1977-08-13 | 1985-04-18 | 2,6-BIS-HALOGENACYLAMINO-BENZO (1,2-D: 5,4-D [) - BISTIAZOLE DERIVATIVES SUCH AS INTERMEDIATES FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2,6-BISAMINOBINZO- (1,2-D: 5, 4-D [) bisthiazole derivative. |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO159277C (en) |
-
1985
- 1985-04-18 NO NO851549A patent/NO159277C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO851549L (en) | 1979-02-14 |
| NO159277C (en) | 1988-12-14 |
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