HU205753B - Process for producing 1,2,5-thiadiazole-1-oxide and -1,1-dioxide derivatives used as intermediary product - Google Patents

Process for producing 1,2,5-thiadiazole-1-oxide and -1,1-dioxide derivatives used as intermediary product Download PDF

Info

Publication number
HU205753B
HU205753B HU893724A HU372480A HU205753B HU 205753 B HU205753 B HU 205753B HU 893724 A HU893724 A HU 893724A HU 372480 A HU372480 A HU 372480A HU 205753 B HU205753 B HU 205753B
Authority
HU
Hungary
Prior art keywords
thiadiazole
oxide
alkyl
formula
dioxide
Prior art date
Application number
HU893724A
Other languages
Hungarian (hu)
Other versions
HUT57755A (en
Inventor
Ronnie Ray Crenshaw
Aldo Antonio Algieri
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of HUT57755A publication Critical patent/HUT57755A/en
Publication of HU205753B publication Critical patent/HU205753B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/08—1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings 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
    • C07D277/38—Nitrogen atoms
    • C07D277/40—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings 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
    • C07D277/38—Nitrogen atoms
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings 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
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings 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
    • C07D277/56—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
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
    • 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
    • C07D307/38—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The title compds. of formula (I) and their non-toxic salts or hydrates are prepd. by treating compds. of formula (II); in the presence of an inactive solvent, with compds. of formulas (A) and (B) , successively. In the formulas, P is 1 or 2; R1 is -NR2R3; R2 and R3 are H, (lower)alkyl, (lower) alkenyl, etc.; m is 0 or 1; n is 2 or 3; Z is S, O or methylene; A is phenyl, imidazolyl, pyridyl, etc; and R7 is halo, (lower)alkyl, (lower) alkylthio, phenoxy, etc. The prods. are useful as antiulcer agents.

Description

A találmány tárgya eljárás közbenső termékként alkalmazott (XXXIX) általános képletű. új 1,2,5-tiadiazol-l-oxid és -1,1-dioxid-származékok előállítására.The present invention relates to a process for the preparation of intermediate XXXIX. for the preparation of new 1,2,5-thiadiazole 1-oxide and -1,1-dioxide derivatives.

E vegyületek az új, hisztamin-H2-antagonista hatású, (I) általános képletű 1,2,5-tíadiazol-származékok előállítására alkalmazhatók (ld. T/29366 magyar közzétett bejelentés).These compounds are useful in the preparation of novel 1,2,5-thiadiazole derivatives of the formula I having histamine H 2 antagonist activity.

A (XXXIX) általános képletben a szubsztituensek jelentése az alábbi:In the formula (XXXIX), the substituents have the following meanings:

R7 jelentése 1-4 szénatomos alkoxicsoport,R 7 is C 1-4 alkoxy,

R12 jelentése A-S-B-általános képletű csoport, amelybenR 12 is a group of formula ASB wherein

A jelentése (1-4 szénatomos alkil)-imidazol-(l vagy 2 szénatomos alkil)-csoport vagy di(l—4 szénatomos alkil)-amino-(l-4 szénatomos alkil)-furil-(l vagy 2 szénatomos alkil)-csoport, ésA is (C 1 -C 4 alkyl) imidazole (C 1 or C 2 alkyl) or di (C 1 -C 4 alkyl) amino (C 1 -C 4 alkyl) furyl (C 1 or C 2 alkyl) and

B jelentése 2-4 szénatomos alkilén-amino-csoport, p jelentése 1 vagy 2.B is a C 2 -C 4 alkylene amino group, p is 1 or 2.

A találmány szerinti új köztitermékek előállítása során úgy járunk el, hogy egy (XXXVIII) általános képletű 3,4-di(l-4 szénatomos alkoxi)-l,2,5-tiadiazol-l-oxid-vagy-l,l-dioxid-származékot—aképletben R7 jelentése 1-4 szénatomos alkoxicsoport; p jelentése 1 vagy 2 — egy A-S-B-H általános képletű aminnal — a képletben A és B jelentése a fenti — reagáltatunk.In the preparation of the novel intermediates of the present invention, a 3,4-di (C 1 -C 4 alkoxy) -1,2,5-thiadiazole-1-oxide or 1,1-dioxide of formula XXXVIII is prepared. a derivative - wherein R 7 is C 1-4 alkoxy; p is 1 or 2 with an amine of formula ASBH wherein A and B are as defined above.

A (XXXVHI) általános képletű azon kiindulási anyagok előállítását, ahol p=l, részletesen ismerteti a 912/85 alapszámú T/52490 számon közzétett magyar szabadalmi bejelentésünk, a dioxidok ismertek (ld. a későbbihivatkozást).The preparation of starting materials of formula (XXXVHI) where p = 1 is described in detail in our Hungarian Patent Application Publication No. 912/85, T / 52490, the dioxides are known (see later).

Az (I) általános képletű vegyületek a (XXXIX) általános képletű vegyületekből kiindulva külöböző módokon állíthatók elő; ezeket részletesen ismertetjük 2170/80 alapszámú, T/29366 számon közzétett magyar szabadalmi bejelentésünkben.The compounds of formula (I) may be prepared from the compounds of formula (XXXIX) in a variety of ways; these are described in detail in our Hungarian Patent Application Publication No. 2170/80, Publication No. T / 29366.

Atalálmányt a továbbiakban—a találmány oltalmi körének szűkítése nélkül—példákkal szemléltetjük.The invention will now be illustrated by the following non-limiting examples.

J, példaExample J

3-{2-[(5-Metil-lH-im.dazol-4-il)-metil-tio]etil-amno}-4-metoxi-l,2,5-tiadiazol-l,i-dioxid előállításaPreparation of 3- {2 - [(5-Methyl-1H-imidazol-4-yl) methylthio] ethylamino} -4-methoxy-1,2,5-thiadiazole-1,1-dioxide

AJ. Org. Chem., 40,2743 (1975) közlemény szerint előállítQtt 3,4-dimetoxi-,2,5-tiadiazol-l,l-dioxid 2,0 g-ját (11,2 mM), 200 ml metanolban szuszpendáljuk, a szuszpenzióhoz erőteljes keverés közben, szobahőmérsékleten 2,73 g (11,2 mM), 25 ml metanolban oldott 2-[(5-metil-lH-imidazol-4-ü)-metü-tio]-etüamint adunk (amit a 779 775 számú belga szabadalmi leírás szerint állítunk elő). 30 percen át keverjük a reakcióelegyet, miután megkapjuk a 3-{2-[(5-metiI-lHimidazol-4-il)-metil-tio]-etil-amino}-4-metoxi-l,2,5 -tiadiazol-l,l-dioxid metanolos oldatát.AJ. Org. Chem., 40, 2743 (1975), 2.0 g (11.2 mM) of 3,4-dimethoxy, 2,5-thiadiazole-1,1-dioxide was suspended in 200 ml of methanol to form a suspension. 2.73 g (11.2 mM) of 2 - [(5-methyl-1H-imidazol-4-yl) methylthio] ethylamine (779 775) in 25 ml of methanol are added with vigorous stirring at room temperature. Belgian patent). Stir the reaction for 30 minutes to obtain 3- {2 - [(5-methyl-1H-imidazol-4-yl) methylthio] ethylamino} -4-methoxy-1,2,5-thiadiazole. 1,1-dioxide in methanol.

A szilikagélen végzett vékonyréteg-kromatográfiás vizsgálat szerint a futtatást diklór-metán és metanol 90:10 arányú elegyével végezve, azRf-érték: 0,44.TLC on silica gel, eluting with 90:10 dichloromethane: methanol, R f = 0.44.

2. példaExample 2

A 3,4-dimetoxi-l,2,5-tiadiazol-l-oxid előállításaPreparation of 3,4-dimethoxy-1,2,5-thiadiazole-1-oxide

100 ml kloroformban feloldunk 35,2g (24,1 mM) a J. Org. Chem., 40, 2749 (1975) közleményben megadottak szerint előállított 3,4-dimetoxi-l,2,5-tiadiazolt, az oldatot 3 perc alatt 50,7 g (25,0 mM, 85 százalék) 900 ml, 20 °C hőmérsékletű kloroformban oldott m-klór-perbenzoesavhoz adjuk keverés közben, miközben a reakcióedényt hűtőfürdőben tartjuk, hogy a hőmérséklet ne emelkedjen 32 ’C fölé az exoterm reakció következtében. 3 órán át szobahőmérsékleten keverjük a reakciőelegyet, a fölös persavreagáltatására további 2,0 g 3,4-dimetoxi-l,2,5-tiadiazoIt adagolunk, majd 1 óránátfolytatjukakeverést.35.2 g (24.1 mM) of J. Org. Chem., 40, 2749 (1975), 3,4-Dimethoxy-1,2,5-thiadiazole, prepared in 50 minutes (50.7 g, 25.0 mM, 85%) in 900 ml at 20 ° C. It is added to m-chloroperbenzoic acid dissolved in chloroform C with stirring while the reaction vessel is kept in a cooling bath so that the temperature does not rise above 32 ° C due to the exothermic reaction. After stirring for 3 hours at room temperature, an additional 2.0 g of 3,4-dimethoxy-1,2,5-thiadiazole was added, followed by stirring for 1 hour.

2x300 ml 1 százalékos nátrium-hidrogén-karbonát-oldattal extraháljuk a szerves oldószeres oldatot, 250 ml vízzel mossuk, vízmentesítjük és csökkentett nyomáson desztilláljuk, miután 47,0 g terméket kapunk. Ezt izopropanolból átkristályosítva 4,0 g 3,4-dimetoxi-l,2,5-tiadiazol-l-oxidot kapunk. A terméket izopropil-alkoholból ismét kikristályosítjuk, amiutn 135-137 ’C hőmérsékleten olvadó analitikai mintát kapunk.The organic solvent solution was extracted with 2 x 300 ml of a 1% sodium bicarbonate solution, washed with 250 ml of water, dried and distilled under reduced pressure to obtain 47.0 g of product. This is recrystallized from isopropanol to give 4.0 g of 3,4-dimethoxy-1,2,5-thiadiazole 1-oxide. The product was recrystallized from isopropyl alcohol to give an analytical sample melting at 135-137 ° C.

Elemanalízis a C4H6N2O3S képlet alapján: számított: C: 29,63, H: 3,72; N: 17,27; S: 19,77%, talált: C:29,53; H: 3,75; N: 17,26; S: 19,83%.Elemental Analysis for: C 4 H 6 N 2 O 3 S Calculated: C, 29.63; H, 3.72; N: 17.27; S, 19.77. Found: C, 29.53; H, 3.75; N: 17.26; S, 19.83%.

3. példaExample 3

A 3-{2-[(5-dimetilaminometil-2-furil)-metiltio]-etil-amino]-4-metoxi-l,2,5-tiadiazoTl,l-diox id előállításaPreparation of 3- {2 - [(5-dimethylaminomethyl-2-furyl) methylthio] ethylamino] -4-methoxy-1,2,5-thiadiazol-1,1-dioxide

A 857 388 számú belga szabadalmi leírás szerint előállított 2-[(5-dimetilaminometil-2-furil)-metiltioj-etil-amin 2,41 g-ját (11,2 mM) 20 ml vízmentes metanolban oldjuk, az oldatot egy adagban 2,0 g (1 l,2mM) 200 ml metanolban szuszpendált 3,4-dimetoxi-l,2,5-tiadiazol-l,I-dioxidhoz adjuk erőteljes keverés közben, 8 ’C hőmérsékleten. 15 percen át 810 ’C hőmérsékleten keverjük a reakcióelegyet, amiután megkapjuk az előállítani kívántvegyület metanolos oldatát.2.41 g (11.2 mM) of 2 - [(5-dimethylaminomethyl-2-furyl) methylthioethylamine, prepared according to Belgian Patent No. 857,388, is dissolved in 20 ml of anhydrous methanol. Add 0 g (1 L, 2 mM) of 3,4-dimethoxy-1,2,5-thiadiazole-1,1-dioxide suspended in 200 mL of methanol at 8 ° C with vigorous stirring. The reaction mixture was stirred at 810 C for 15 minutes to give a methanolic solution of the desired compound.

4. péláaExample 4

A 3-{2-[(5-dimetilaminometil-2-furil)-metiltio}-etil-amino]-4-metoxi-1,2,5-tiadiazol-1,1dioxid előállítása ml vízmentes metanolban 2,14 g (10,0 mM) 2[(5-dimetilaminometil-2-furil)-metil-tio]-etil-amint oldunk, az oldatot cseppenként, erőteljes keverés közben, 35perc alatt 1,78 g (10,0 mM), 180 ml, jeges vízfürdőben 1 ’C hőmérsékletre hűtött vízmentes metanolban szuszpendált 3,4-dimetoxi-l,2,5-tiadiazol1,1-dioxidhoz adjuk. 15 percen át 0 ’C hőmérsékleten tartjuk az elegyet, miután megkapjuk a tennék metanolos oldatát.Preparation of 3- {2 - [(5-dimethylaminomethyl-2-furyl) methylthio} ethylamino] -4-methoxy-1,2,5-thiadiazole-1,1-dioxide in ml of anhydrous methanol 0mM) of 2 - [(5-dimethylaminomethyl-2-furyl) -methylthio] -ethylamine was dissolved in 1.78 g (10.0 mM), 180 ml, dropwise over 35 minutes with vigorous stirring. is added to 3,4-dimethoxy-1,2,5-thiadiazole-1,1-dioxide suspended in anhydrous methanol cooled to 1 ° C in an ice-water bath. After 15 minutes at 0 ° C, a methanolic solution of the product was obtained.

A termék szilikagéles vékonyrétegkromatográfiás Rf-értéke 0,48 (diklór-metán és metanol 9:1 arányú elegye).The product had an Rf value of 0.48 (9: 1 dichloromethane: methanol).

6,0 n hidrogén-klorid-oldattal savasra állítjuk be 2,0 ml fenti oldat pH-ját, majd melegítés nélkül, csökkentett nyomáson desztilláljuk az oldatot, fiy módon6.0 N hydrochloric acid is acidified to pH 2.0 with 2.0 ml of the above solution, and the solution is distilled under reduced pressure without heating.

1,1

HU 205753 Β megkapjuk a termék hidrogén-kloridos sóját.EN 205753 Β the hydrochloride salt of the product is obtained.

A vegyület D2Ö-ben felvett mágneses magrezonancia spektruma (100 MHz) a következő:The compounds recorded in D 2 O-nuclear magnetic resonance spectrum (100 MHz) the following:

d: 6,45 (d, IH); 6,19 (d, IH); 4,14 (s, 2H); 4,0 (s, 3H);d: 6.45 (d, 1H); 6.19 (d, 1H); 4.14 (s, 2H); 4.0 (s, 3H);

3,64 (s, 2H); 3,37 (t, 2H); 2,65 (s, 6H); 2,61 (t, 2H). 53.64 (s, 2H); 3.37 (t, 2H); 2.65 (s, 6H); 2.61 (t, 2H). 5

5. példaExample 5

3-{2-[(5-dimetilaminometil-2-furil)-metil-tio] -etil-antinoj-4-metoxi-l,2,5-tiadiazol-l-oxid elő-, állítása 10 ml metanolban 3,30 g (15,4 mM) 2-[(5-dimetilaminometil-2-furil)-metil-tio]-etil-amint oldunk, az oldatot cseppenként, 14 perc alat 2,50 g (15,4 mM), aPreparation of 3- {2 - [(5-dimethylaminomethyl-2-furyl) -methyl-thio] -ethyl-antino-4-methoxy-1,2,5-thiadiazole-1-oxide in 10 ml of methanol 3.30 2 - [(5-Dimethylaminomethyl-2-furyl) -methylthio] -ethylamine (15.4 mM) was dissolved in 2.50 g (15.4 mM) dropwise over a period of 14 minutes.

2. példa szerint előállított 3,4-dimetoxi-l,2,5-tiadiazol-l-oxid jeges-vizes fürdőben 12-15 °C hőmérsék- 15 letre hűtött és erőteljesen kevert szuszpenziójához adjuk. 1,5 órán át szobahőmérsékleten keverjük az oldatot, miután megkapjuk a termék metanolos oldatát.The suspension of 3,4-dimethoxy-1,2,5-thiadiazole-1-oxide prepared in Example 2 was added to an ice-water bath cooled to 12-15 ° C with vigorous stirring. The solution was stirred at room temperature for 1.5 hours after obtaining a methanolic solution of the product.

Claims (1)

SZABADALMI IGÉNYPONTPatent Claim Point Eljárás (ΧΧΧΓΧ) általános képletű 1,2,5-tiadiazol1-oxid- és -1,1-dioxid-származékok elállítására — a képletbenA process for the preparation of 1,2,5-thiadiazole 1-oxide and -1,1-dioxide derivatives of the general formula ΧΧΧΓΧ R7 jelentése 1-4 szénatomos alkoxicsoport,R 7 is C 1-4 alkoxy, R12 jelentése A-S-B-általános képletű csoport, amelybenR 12 is a group of formula ASB wherein A jelentése (1-4 szénatomos alkil)-imidazol-(l vagy 2 szénatomos alkil)-csoport vagy di(l~4 szénatomos alkil)-amino-(l-4 szénatomos alkil)-furil-(l vagy 2 szénatomos alkil)-csoport, ésA is (C 1 -C 4 alkyl) imidazole (C 1 or C 2 alkyl) or di (C 1 -C 4 alkyl) amino (C 1 -C 4 alkyl) furyl (C 1 or C 2 alkyl) and B jelentése 2-4 szénatomos alkilén-amino-csoport, p jelentése 1 vagy 2— azzal jellemezve, hogy egy (XXXVBI) általános képletű 3,4-di(l-4 szénatomos alkoxi)-l,2,5-tiadiazol1-oxid- vagy -1,1-dioxid-származékot — a képletben R7 jelentése 1 -4 szénatomos alkoxicsoport, p jelentése 1 vagy 2—egy A-S-B-H általános képletű aminnal—a képletben A és B jelentése a tárgyi körben megadott— reagáltatunk.B is a C 2 -C 4 alkylene amino group, p is 1 or 2 - characterized in that a 3,4-di (C 1 -C 4 alkoxy) -1,2,5-thiadiazole 1-oxide of formula (XXXVBI) or a -1,1-dioxide derivative wherein R 7 is C 1 -C 4 alkoxy, p is 1 or 2 with an amine of formula ASBH - wherein A and B are as defined herein.
HU893724A 1979-09-04 1980-09-03 Process for producing 1,2,5-thiadiazole-1-oxide and -1,1-dioxide derivatives used as intermediary product HU205753B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US7251779A 1979-09-04 1979-09-04

Publications (2)

Publication Number Publication Date
HUT57755A HUT57755A (en) 1991-12-30
HU205753B true HU205753B (en) 1992-06-29

Family

ID=22108102

Family Applications (2)

Application Number Title Priority Date Filing Date
HU85912A HU201539B (en) 1979-09-04 1980-09-03 Process for production of derivatives of 1,2,5-tiadiasole-1-oxid applicable as intermedier
HU893724A HU205753B (en) 1979-09-04 1980-09-03 Process for producing 1,2,5-thiadiazole-1-oxide and -1,1-dioxide derivatives used as intermediary product

Family Applications Before (1)

Application Number Title Priority Date Filing Date
HU85912A HU201539B (en) 1979-09-04 1980-09-03 Process for production of derivatives of 1,2,5-tiadiasole-1-oxid applicable as intermedier

Country Status (11)

Country Link
JP (1) JPS63211272A (en)
KR (1) KR850000759B1 (en)
AT (1) AT380019B (en)
AU (2) AU541849B2 (en)
BE (1) BE885089A (en)
CS (2) CS221977B2 (en)
FR (2) FR2476081A1 (en)
GR (1) GR70020B (en)
HU (2) HU201539B (en)
YU (2) YU41941B (en)
ZA (1) ZA805250B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3175201D1 (en) * 1980-04-30 1986-10-02 Merck & Co Inc Aminothiadiazoles as gastric secretion inhibitors

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL22850A (en) * 1964-03-18 1968-12-26 Merck & Co Inc 3-chloro-1,2,5-thiazdiazole-4-carboxylic acid being an intermediate in the preparation of sulfa drugs
CH482712A (en) * 1964-10-01 1969-12-15 Merck & Co Inc Process for the preparation of 3-amino-1,2,5-thiadiazoles
DE1770152A1 (en) * 1968-04-08 1971-09-30 Lentia Gmbh Process for the preparation of 3-amino-4-bromo-1,2,5-thiadiazole
US3657237A (en) * 1968-05-22 1972-04-18 Frosst & Co Charles E Process for making 1 2 5-thiadiazoles in the sinister configuration
AT348517B (en) * 1977-01-19 1979-02-26 Chemie Linz Ag PROCESS FOR THE PREPARATION OF PURE 3-METHOXY-4- (4'-AMINOBENZOLSULFONAMIDO) -1,2,5-THIADIAZOLE
DE3175201D1 (en) * 1980-04-30 1986-10-02 Merck & Co Inc Aminothiadiazoles as gastric secretion inhibitors

Also Published As

Publication number Publication date
ATA64684A (en) 1985-08-15
JPS63211272A (en) 1988-09-02
FR2486528B1 (en) 1984-12-21
FR2486528A1 (en) 1982-01-15
YU41941B (en) 1988-02-29
AU563856B2 (en) 1987-07-23
FR2476081A1 (en) 1981-08-21
KR850000759B1 (en) 1985-05-25
HU201539B (en) 1990-11-28
BE885089A (en) 1981-03-04
CS246052B2 (en) 1986-10-16
AU541849B2 (en) 1985-01-24
YU213280A (en) 1983-06-30
ZA805250B (en) 1981-09-30
KR830003434A (en) 1983-06-20
FR2476081B1 (en) 1985-04-12
HUT57755A (en) 1991-12-30
AT380019B (en) 1986-03-25
CS221977B2 (en) 1983-04-29
AU3539684A (en) 1985-03-14
GR70020B (en) 1982-07-23
YU9483A (en) 1983-06-30
AU6194280A (en) 1981-03-12

Similar Documents

Publication Publication Date Title
RU1836362C (en) A method for obtaining 5-[2-(4- aminophenyl)ethenyl] -5,6-dihydro-1,3,4 -thiadiazine-2- (3h)-ones
FI59991B (en) PROCEDURE FOR THE FRAMSTATION OF AV 2-ARYLAMINO-2-IMIDAZOLINE DERIVATIVES AND DERAS SALTER
TOMINAGA et al. Studies on positive inotropic agents. I. Synthesis of 3, 4-dihydro-6-[4-(3, 4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H)-quinolinone and related compounds
FI63573C (en) FREEZING FOR OXIBENSOTIAZINE DIOXIDERS CABOXAMIDERS
CZ291857B6 (en) Process for preparing 3-amino-2-mercaptobenzoic acid derivatives, the derivatives per se and intermediates used in this process
JP2505531B2 (en) Process for producing 3-cyano-4-aryl-pyrroles
PL117998B1 (en) Process for preparing novel 2-nitroaminopyrimidones
US4255565A (en) Production of 2,6-diaminonebularines
JPH09501175A (en) Process for producing fluoroatenylthioheterocycle derivative
PL163313B1 (en) Method of obtaining derivatives of guanine
JP2000204085A (en) Isothiazole carboxylic acid derivative and disease controlling agent
US5552557A (en) Process for preparing 2-cyanoimidazole compounds by reaction of an amino ketone compound
Ram et al. Chemotherapeutic agents. IX. Synthesis and pesticidal activities of bis [4‐aryl/alkyl‐1, 2, 4‐triazoline‐5‐thione‐3‐yl] alkanes and 1‐Aryl/alkyl‐3‐[4‐(4‐aryl/alkyl‐1, 2, 4‐triazoline‐5‐thione‐3‐yl) phenyl] thiourea and related compounds
HU205753B (en) Process for producing 1,2,5-thiadiazole-1-oxide and -1,1-dioxide derivatives used as intermediary product
US5840922A (en) Coumarin derivatives, and processes for their preparation
US4267343A (en) Process for the manufacture of 2,5-bis-(benzoxazolyl)-thiophene compounds
US4025537A (en) Preparation of 3-carboalkoxy or 3-alkanoyl furans
US5446154A (en) Process for the preparation of aminotriazine derivatives
FR2481280A1 (en) PROCESS FOR THE PREPARATION OF 2-GUANIDINOTHIAZOLE DERIVATIVES, NOVEL PRODUCTS THUS OBTAINED AND THEIR USE AS AGENTS AGAINST STOMACH ULCERS
HU212611B (en) Process for the preparation of 2-substituted 4,6-dialkoxy-pyrimidine derivatives
RU2786442C1 (en) Substituted o-alkyl-2-arylhydrazine carbotioates and method for their preparation
US4603227A (en) Novel process for preparing α-(trichloromethyl)benzyl alcohols from benzaldehydes
US4071684A (en) Process for producing 3-substituted 1,2,4-triazines
JPH0710857B2 (en) Intermediate compound
US4658025A (en) Hydrazine-thiocarboxylic acid O-carbamoylmethyl esters

Legal Events

Date Code Title Description
HMM4 Cancellation of final prot. due to non-payment of fee