NO124374B - - Google Patents
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- NO124374B NO124374B NO2659/69A NO265969A NO124374B NO 124374 B NO124374 B NO 124374B NO 2659/69 A NO2659/69 A NO 2659/69A NO 265969 A NO265969 A NO 265969A NO 124374 B NO124374 B NO 124374B
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- general formula
- denotes
- compound
- carbon atoms
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- 150000001875 compounds Chemical class 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 150000003456 sulfonamides Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 229940124530 sulfonamide Drugs 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical class O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229940118019 malondialdehyde Drugs 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 2
- XMVNMWDLOGSUSM-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=NO1 XMVNMWDLOGSUSM-UHFFFAOYSA-N 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- OIEZCWFCXVSIGQ-UHFFFAOYSA-N 1,1-diethoxy-4-methylpentane Chemical compound CCOC(OCC)CCC(C)C OIEZCWFCXVSIGQ-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- ZINCSSQSZVBPDS-UHFFFAOYSA-N 2-chloro-5-propan-2-yloxypyrimidine Chemical compound CC(C)OC1=CN=C(Cl)N=C1 ZINCSSQSZVBPDS-UHFFFAOYSA-N 0.000 description 1
- YAKIJEZSDKOGGQ-UHFFFAOYSA-N 5-(2-methylpropyl)pyrimidin-2-amine Chemical compound CC(C)CC1=CN=C(N)N=C1 YAKIJEZSDKOGGQ-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- -1 aldehyde acetals Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
- 229960004111 buformin Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Analogifremgangsmåte ved fremstilling av Analogy method in the production of
blodsukkersenkende sulfonamider. blood sugar-lowering sulfonamides.
Foreliggende oppfinnelse angår en analogifremgangsmåte ved fremstilling av blodsukkersenkende sulfonamider av den generelle formel: The present invention relates to an analogous method for the production of blood sugar-lowering sulfonamides of the general formula:
hvor og R er like eller forskjellige og betegner hydrogen- eller where and R are the same or different and denote hydrogen or
halogenatomer eller alkyl- eller alkylthiogrupper med 1-4 carbonato-m& t, fig betegner en alkyl-, alkoxy- eller alkoxyalkoxygruppe som inne-holder 1-8 carbonatomer, R^ betegner et hydrogenatom eller en alkyl- halogen atoms or alkyl or alkylthio groups with 1 to 4 carbon atoms, fig denotes an alkyl, alkoxy or alkoxy alkoxy group containing 1 to 8 carbon atoms, R denotes a hydrogen atom or an alkyl
gruppe med 1-4 carbonatomer, X betegner et oxygen-, nitrogen- eller svovelatom, Y betegner en alkylgruppe med 1-4 carbonatomer og n betegner et helt tall fra O til 4, og deres salter med fysiologisk forlikelige baser. group with 1-4 carbon atoms, X denotes an oxygen, nitrogen or sulfur atom, Y denotes an alkyl group with 1-4 carbon atoms and n denotes an integer from O to 4, and their salts with physiologically compatible bases.
De nye forbindelser har meget god virkning som antidiabet-ika. Således frembringer de nye. forbindelser ved anvendelse p-å--rotter i doser av- 0,1 - 1,0 mg/kg kroppsvekt efter standardmetodene en senk-ning av blodsukkerinnh-oldet med inntil over 35 % av utgangsverdien. The new compounds have a very good effect as antidiabetics. Thus they produce new ones. compounds when applied to rats in doses of 0.1 - 1.0 mg/kg body weight according to the standard methods a lowering of the blood sugar content by up to more than 35% of the initial value.
For terapeutisk anvendelse kan de nye forbindelser benyt-tes som frie sulfonamider eller som salter med fysiologisk forlikelige baser. Som baser kan der f.eks. anvendes natriumhydroxyd, lithium-hydroxyd, kalsiumhydroxyd eller ammoniumhydroxyd eller aminer, såsom methylglucamin, morfolin- eller ethanolamin. Også blandinger av de frie sulfonamider med et egnet alkalicarbonat eller -hydrogencarbonat kan anvendes. Av særlig interesse er salter av sulfonamider med baser, som selv oppviser blodsukkersenkende virkning, såsom f.eks. butylbigu-anid. For therapeutic use, the new compounds can be used as free sulfonamides or as salts with physiologically compatible bases. As bases, there can e.g. sodium hydroxide, lithium hydroxide, calcium hydroxide or ammonium hydroxide or amines such as methylglucamine, morpholine or ethanolamine are used. Mixtures of the free sulphonamides with a suitable alkali carbonate or hydrogen carbonate can also be used. Of particular interest are salts of sulfonamides with bases, which themselves exhibit a blood sugar-lowering effect, such as e.g. butyl bigu-anide.
De nye forbindelser kan administreres sammen med eller uten de i den galeniske farmasi vanlige tilsetningsmidler, bærersub-stanser, smaksstoffer, osv. og således administreres f.eks. i pulver-form eller i form av tabletter, dfageer, kapsler, piller, suspensjoner eller opplosninger. The new compounds can be administered together with or without the usual additives, carrier substances, flavorings, etc. in galenic pharmacy and thus administered e.g. in powder form or in the form of tablets, phages, capsules, pills, suspensions or solutions.
De nye sulfonamider kan fremstilles ved at The new sulfonamides can be prepared by
a) en forbindelse av den generelle formel: a) a compound of the general formula:
hvor R^, R2, R4, n, X og Y har de ovenfor angitte betydninger, kondenseres under ringslutning med et substituert malondialdehyd av den generelle formel: where R 1 , R 2 , R 4 , n, X and Y have the meanings given above, is condensed during ring closure with a substituted malondialdehyde of the general formula:
hvor R 3 har den ovenfor angitte betydning, og hvor aldehydgruppene dessuten kan være funksjonelt omdannet, eller where R 3 has the meaning stated above, and where the aldehyde groups can also be functionally converted, or
b) en forbindelse av den generelle formel: b) a compound of the general formula:
hvor R^, R^, R4, n, X og Y har de ovenfor angitte betydninger, omsettes i den frie form eller i form av et alkalisalt med en forbindelse av den generelle formel: where R^, R^, R4, n, X and Y have the meanings given above, is reacted in the free form or in the form of an alkali salt with a compound of the general formula:
hvor R^ har den ovenfor angitte betydning og L betegner ét halogenatom, fortrinnsvis klor, en trialkylammoniumgruppe eller en lavere alkylsul-fonylgruppe, eller where R^ has the above-mentioned meaning and L denotes one halogen atom, preferably chlorine, a trialkylammonium group or a lower alkylsulfonyl group, or
c) en forbindelse av den generelle formel: c) a compound of the general formula:
hvor R^, R^, n og X har de ovenfor angitte betydninger, eller et ekvi-valent reaktivt derivat av den tilsvarende syre omsettes med et amin av den generelle formel: where R^, R^, n and X have the meanings given above, or an equivalent reactive derivative of the corresponding acid is reacted with an amine of the general formula:
hvor where
R^ og R^ har de ovenfor angitte betydninger, R^ and R^ have the meanings indicated above,
og forbindelsen fremstillet efter den ene eller den annen av de angitte metoder om onskes overfores til et salt med en fysiologisk forlikelig base. and the compound prepared according to one or the other of the indicated methods is, if desired, converted into a salt with a physiologically compatible base.
De ved omsetningen ifolge metode a) anvendte malonalde-hydderivater kan fremstilles ved at man efter kjente metoder formyle-rer aldehydacetaler av den generelle formel: The malonaldehyde derivatives used in the reaction according to method a) can be prepared by formylating aldehyde acetals of the general formula according to known methods:
hvor R<*>" betegner en lavere eller midlere alkylgruppe. where R<*>" denotes a lower or middle alkyl group.
Eksempel 1 Example 1
33 g 2- (4-(3-aminoethylbenzensulf onamido) -5-isobutylpyrimi-din (fremstillet ved omsetning av carfoethoxyaminoethylbenzensulfoklor-id med 2-amino-5-isobutylpyrimidin og påfolgende forsåpning av carb-ethoxyamirroethylgruppen til en aminoethylgruppe; smeltepunkt 223°C) pppldses i lOO ml pyridin og oppvarmes efter tilsetning av 16 g 5-roethylisoxazol-3-carboxylsyreklorid i 2 timer ved 60°C. Pyridinet avdestilleres derefter, og residuet tilsettes vann. Efter surgjoring med saltsyre frafiltreres. utfellingen, hvorefter denne omkrystallise-res fra methylglycol. Der erholdes således 30 g 2-[4-(5-methylisox-azolyl-3-carbonamido)-ethylbenzensulfonamido]-5-isobutylpyrimidin med smeltepunkt 223°C. 33 g of 2-(4-(3-aminoethylbenzenesulfonamido)-5-isobutylpyrimidine (produced by reacting carphoethoxyaminoethylbenzenesulfochloride with 2-amino-5-isobutylpyrimidine and subsequent saponification of the carb-ethoxyamiroethyl group to an aminoethyl group; melting point 223°C ) is dissolved in 100 ml of pyridine and heated after adding 16 g of 5-roethylisoxazole-3-carboxylic acid chloride for 2 hours at 60° C. The pyridine is then distilled off, and the residue is added to water. After acidification with hydrochloric acid, the precipitate is filtered off, after which it is recrystallized 30 g of 2-[4-(5-methylisox-azolyl-3-carbonamido)-ethylbenzenesulfonamido]-5-isobutylpyrimidine with a melting point of 223°C are thus obtained.
På tilsvarende måte erholdes ved anvendelse av de tilsvarende utgangsmaterialer: 2-[4-(5-methylisoxazol-3-carbonamido)-ethylbenzensulfonamido]-5-n-but-oxypyrimidin, med smeltepunkt 195°e,. The following is obtained in a similar manner by using the corresponding starting materials: 2-[4-(5-methylisoxazol-3-carbonamido)-ethylbenzenesulfonamido]-5-n-but-oxypyrimidine, with melting point 195°e.
2-[4-(5-methylis oxazol-3-carbonamido)-ethylbenzensulfonamido]-5-is o-propoxypyrimidin, med smeltepunkt 221°C, 2-[4-(5-methylis oxazol-3-carbonamido)-ethylbenzensulfonamido]-5-meth-oxyethoxypyrimidin, med smeltepunkt 205°C, 2-[4-(5-methylis oxazol-3-carbonamido)-ethylbenzenesulfonamido]-5-is o-propoxypyrimidine, with melting point 221°C, 2-[4-(5-methylis oxazol-3-carbonamido)-ethylbenzenesulfonamido] -5-meth-oxyethoxypyrimidine, with melting point 205°C,
2- [4- (5-methylis"oxazol-3-carbonamido) -methylbenzerisulf onamido]-5-iso-butylpyrimidin, med smeLtepunkt 253°C, 2-[4-(3,5-bis-methylthioisothiazolyl-4-carboxy)-aminoethylbenzensulf-onylamido]-5-n-propoxypyrimidin, med smeltepunkt 182°C, 2-[4-(3,4-diklorisothiazol-5-carbonamido)-ethylbenzensulfonamido]-5-isopropoxypyrimidin, mod smeltepunkt 202 - 203°C, 2-[4-(5-methylisoxazol-3-carbonamido)-methylbenzerisulfonamido]-5-isobutylpyrimidine, melting point 253°C, 2-[4-(3,5-bis-methylthioisothiazolyl-4-carboxy )-aminoethylbenzenesulfonylamido]-5-n-propoxypyrimidine, with melting point 182°C, 2-[4-(3,4-dichloroisothiazol-5-carbonamido)-ethylbenzenesulfonamido]-5-isopropoxypyrimidine, with melting point 202 - 203°C ,
2-[4-(4-klor-5-methylisoxazol-3-carbonamido)-ethylbenzensulfonamido]-5-isopropoxypyrimidin, med smeltepunkt 138°C. 2-[4-(4-chloro-5-methylisoxazole-3-carbonamido)-ethylbenzenesulfonamido]-5-isopropoxypyrimidine, with melting point 138°C.
Eksempel 2 Example 2
35 g 4-(3-methylpyrazol-5-carbonyIamino)-ethylbenzensulfo-guanidin (smeltepunkt 268°C) oppvarmes i 5 timer ved koketemperatur sammen med en oppldsning av 16 g a-isobutyl-(3-dimethylaminc-acrolein (fremstillet efter Vilsmeier's metode ut fra isobutylacetaldehyd-di-ethylacetalf kokepunkt 106°C ved 0,03 torr) og 3 g natrium i 250 ml methanol. Methanolen avdestilleres derefter, og residuet opploses i vann. Efter klaring av opplosningen med carbon erholdes ved surgjoring med saltsyre en utfeldning som efter omkrys tallise.ring fra methylglycol består av 29, g 2-[4-(.3-methylpyrazol-5-carbonylamino)-ethylben-zensulf onamido]-5-isobutyIpyrimidin med smeltepunkt 243°C. 35 g of 4-(3-methylpyrazole-5-carbonylamino)-ethylbenzenesulfo-guanidine (melting point 268°C) is heated for 5 hours at boiling temperature together with a solution of 16 g of α-isobutyl-(3-dimethylaminoc-acrolein (prepared according to Vilsmeier's method based on isobutylacetaldehyde-di-ethylacetal (boiling point 106°C at 0.03 torr) and 3 g of sodium in 250 ml of methanol. The methanol is then distilled off, and the residue is dissolved in water. After clarification of the solution with carbon, a precipitate is obtained by acidification with hydrochloric acid which, after recrystallization from methylglycol, consists of 29 g of 2-[4-(.3-methylpyrazol-5-carbonylamino)-ethylbenzenesulfonamido]-5-isobutylpyrimidine with a melting point of 243°C.
Eksempel 3 Example 3
33 g 4-(5-methylisoxazol-3-carbonamido)-ethylbenzensulf-onamidhatrium (smeltepunkt 216°C) opploses i 25Q ral acetamid og omro-res med 16,5 g 2-kIor-5-isopropoxypyrimidin i 6 timer ved 150°C. Acetamidet avdéati Ueres derefter, og residuet tilsettes vann. Der erholdes en utfeldning som efter omkrystallisering fra methylglycol består av 28 g 2-[4-(5-methylisoxazol-3-carbonamido)-ethylbenzensulf-onamido}-5-isopropoxypyrimidin med smeltepunkt 218°C- 33 g of 4-(5-methylisoxazol-3-carbonamido)-ethylbenzenesulfonamide sodium (melting point 216°C) are dissolved in 25% ral acetamide and stirred with 16.5 g of 2-chloro-5-isopropoxypyrimidine for 6 hours at 150° C. The acetamide is then evaporated, and the residue is added to water. A precipitate is obtained which, after recrystallization from methyl glycol, consists of 28 g of 2-[4-(5-methylisoxazol-3-carbonamido)-ethylbenzenesulfonamido}-5-isopropoxypyrimidine with a melting point of 218°C-
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19681770731 DE1770731A1 (en) | 1968-06-27 | 1968-06-27 | New blood sugar lowering sulfonamides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO124374B true NO124374B (en) | 1972-04-10 |
Family
ID=5700618
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2659/69A NO124374B (en) | 1968-06-27 | 1969-06-26 |
Country Status (14)
| Country | Link |
|---|---|
| AT (3) | AT291256B (en) |
| BE (1) | BE735287A (en) |
| BR (1) | BR6908777D0 (en) |
| CH (1) | CH518968A (en) |
| DE (1) | DE1770731A1 (en) |
| DK (1) | DK123602B (en) |
| ES (1) | ES368100A1 (en) |
| FR (1) | FR2014300B1 (en) |
| GB (1) | GB1268835A (en) |
| IE (1) | IE33175B1 (en) |
| IL (1) | IL32396A (en) |
| NL (1) | NL6909960A (en) |
| NO (1) | NO124374B (en) |
| SE (1) | SE357365B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2048906A1 (en) * | 1970-10-06 | 1972-04-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Blood sugar lowering sulfonylaminopyrimidines and processes for their preparation |
| AU2003232551A1 (en) * | 2002-06-13 | 2003-12-31 | Qlt Inc. | Methods of using isothiazole derivatives to treat cancer or inflammation |
-
1968
- 1968-06-27 DE DE19681770731 patent/DE1770731A1/en active Pending
-
1969
- 1969-05-14 BR BR208777/69A patent/BR6908777D0/en unknown
- 1969-06-03 DK DK300869AA patent/DK123602B/en unknown
- 1969-06-05 CH CH860269A patent/CH518968A/en not_active IP Right Cessation
- 1969-06-06 ES ES368100A patent/ES368100A1/en not_active Expired
- 1969-06-13 IL IL32396A patent/IL32396A/en unknown
- 1969-06-16 GB GB30406/69A patent/GB1268835A/en not_active Expired
- 1969-06-17 AT AT788870A patent/AT291256B/en not_active IP Right Cessation
- 1969-06-17 AT AT788770A patent/AT291255B/en not_active IP Right Cessation
- 1969-06-17 AT AT573169A patent/AT289109B/en not_active IP Right Cessation
- 1969-06-24 SE SE08952/69A patent/SE357365B/xx unknown
- 1969-06-25 IE IE873/69A patent/IE33175B1/en unknown
- 1969-06-26 FR FR696921467A patent/FR2014300B1/fr not_active Expired
- 1969-06-26 NO NO2659/69A patent/NO124374B/no unknown
- 1969-06-27 BE BE735287D patent/BE735287A/xx not_active Expired
- 1969-06-27 NL NL6909960A patent/NL6909960A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR2014300A1 (en) | 1970-04-17 |
| BR6908777D0 (en) | 1973-01-23 |
| SE357365B (en) | 1973-06-25 |
| DK123602B (en) | 1972-07-10 |
| GB1268835A (en) | 1972-03-29 |
| DE1770731A1 (en) | 1971-11-25 |
| IL32396A (en) | 1972-06-28 |
| AT291256B (en) | 1971-07-12 |
| IE33175B1 (en) | 1974-04-03 |
| ES368100A1 (en) | 1971-05-01 |
| AT289109B (en) | 1971-04-13 |
| CH518968A (en) | 1972-02-15 |
| AT291255B (en) | 1971-07-12 |
| NL6909960A (en) | 1969-12-30 |
| IL32396A0 (en) | 1969-08-27 |
| BE735287A (en) | 1969-12-29 |
| FR2014300B1 (en) | 1973-01-12 |
| IE33175L (en) | 1969-12-27 |
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