CS272236B2 - Method of -/9-acrydinylamino)-methoxymethanesulphonanilide production - Google Patents
Method of -/9-acrydinylamino)-methoxymethanesulphonanilide production Download PDFInfo
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- CS272236B2 CS272236B2 CS883567A CS356788A CS272236B2 CS 272236 B2 CS272236 B2 CS 272236B2 CS 883567 A CS883567 A CS 883567A CS 356788 A CS356788 A CS 356788A CS 272236 B2 CS272236 B2 CS 272236B2
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- Prior art keywords
- acridinylamino
- water
- acid
- organic solvent
- ethanol
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- 238000000034 method Methods 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- -1 9-acridinylamino Chemical group 0.000 claims description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 7
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 5
- 235000014655 lactic acid Nutrition 0.000 claims description 5
- GVBHRNIWBGTNQA-UHFFFAOYSA-N 2-methoxy-4-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N GVBHRNIWBGTNQA-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- DOXCWSBETLOACP-UHFFFAOYSA-N 2-anilinobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1NC1=CC=CC=C1 DOXCWSBETLOACP-UHFFFAOYSA-N 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 1
- FDPVTENMNDHFNK-UHFFFAOYSA-N 2-amino-n-phenylbenzamide Chemical compound NC1=CC=CC=C1C(=O)NC1=CC=CC=C1 FDPVTENMNDHFNK-UHFFFAOYSA-N 0.000 description 1
- JJCXZGRKDRKMPT-UHFFFAOYSA-N 4-chloroacridine Chemical compound C1=CC=C2N=C3C(Cl)=CC=CC3=CC2=C1 JJCXZGRKDRKMPT-UHFFFAOYSA-N 0.000 description 1
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Předložený vynález ee týká zpOaobu přípravy 4'-{9-akridinylaaino)-3'-methoxyaethan8ulfonanilidu (a - AMSA) vzoroe IThe present invention relates to a process for the preparation of 4 '- (9-acridinylaaino) -3'-methoxyaethane sulfonanilide (α-AMSA) of Formula I
a jeho laktétu» Tyto sloučeniny vykazuji protlnádorový účinek a lze je užit jako léčiva.and its lactate. These compounds have an antitumor effect and can be used as medicaments.
Z amerického patentu č» 4 258 191 je znáa způsob přípravy 4'-(9-akridinylamino)-S^-aethoxymethaneulfonanilidu spočívající v přeměně 4-nitroanieidinu na 4-butyraaido-3-methoxynltrobenzen, ve kterém se potom redukuje nitroskupina a v získaném 4-butyraaido-3-methoxyanilinu sa mesyluje aminoskupina a hydrolyauje butyroekupina, přičemž se získá 4-amino-3-methoxymethansulfonanilid, V posledním stupni ee kondenzuje 4-chlorakridin a 4-amino-3-aethoxymethaneulfonanilidea, Čímž vznikne 4*-(9-akridinylamino)3'-methoxymethansulfonenilid.U.S. Pat. No. 4,258,191 discloses a process for the preparation of 4 '- (9-acridinylamino) -S-4-ethoxymethane sulfonanilide by converting 4-nitroanidine to 4-butyraaido-3-methoxyntrobenzene, in which the nitro group is then reduced and -butyraaido-3-methoxyaniline is mesylated with amino and hydrolyzed with butyro to give 4-amino-3-methoxymethanesulfonanilide. In the final step ee condenses 4-chloroacridine and 4-amino-3-aethoxymethane sulfonanilide to form 4 * - (9-acridines) ) 3'-methoxymethanesulfonenilide.
Nevýhoda tohoto postupu spočivá v tom, že se jako meziprodukt používá 9-chlorakridin,- který působí dráždivě ne pokožku β při přípravě a použiti ve velkém měřítku se snadno hydrolysuje na ekridon e dále v nutnosti chráněná eminoekupiny ve 4-nitro-oanieidinu butyrylovou skupinou a ostradováni této chránící skupiny v posledním stupni, což je nepříjemné.The disadvantage of this process is that 9-chloroacridine is used as an intermediate, which is irritating to the skin β in the preparation and large-scale use, readily hydrolyses to ecridone, further requiring the protected amino group in 4-nitro-oanidin by a butyryl group, and removing this protecting group in the last step, which is annoying.
amerického patentu č. 4 335 244 je znáa způsob přípravy laktátu 4'-(9-akrldinylemino)-3'-methoxymethansulfonanilidu (a<- AMSA). Způeob epočivá v rozpuštění a - AMSA bese v acetonu a v přidáni kyseliny mléčné ke vzniklému roztoku. Při této reakci ee získá krystalický a-AMSA-laktát ve formě solvátů 8 acetonem, které obsahuji aei 0,5 mol acetonu na 1 mol laktátu. Lyofiliaací vodných roztoků heaiacetonátu a-AMSA-laktátu se získá produkt proetý acetonu.U.S. Pat. No. 4,335,244 discloses a process for preparing 4 '- (9-acridinylemino) -3'-methoxymethanesulfonanilide (α-AMSA) lactate. The method of dissolving α-AMSA is in acetone and in the addition of lactic acid to the resulting solution. In this reaction, ee obtains crystalline α-AMSA-lactate in the form of solvates of 8 with acetone containing at least 0.5 moles of acetone per mole of lactate. Lyophilization of aqueous solutions of α-AMSA-lactate heaiacetonate affords acetone-prone product.
Předmětea předloženého vynálezu je způsob přípravy 4*-(9-akridinylasino)-3''-ssthoxyaethansulfonanilidu vzorce IThe subject of the present invention is a process for the preparation of 4 * - (9-acridinylasino) -3 ' - < / RTI >
CHjO .HHSOgCHj (I) a Jeho loktátu, který ee vyznačuje tim, že se chloruje suspenze N-fenylanthranilovó kyeelinyiV aprotické» rozpouštědle a ziekaný chlorid N-fenylanthranilovó kyeeliny se kondenzuje v aprotické» rozpouštědle $ nadbytkea 4-nitro-o-anieidinu za vzniku N -(2-methoxy-4-nitrofenyl)amidu N-fenylanthranilovó kyeeliny vzorce IXCH 2 O.HHSOgCH 3 (I) and its elbow, characterized in that the suspension of the N-phenylanthranilic acid keeline in an aprotic solvent is chlorinated and the foregoing N-phenylanthranilic acid chloride is condensed in an aprotic solvent of excess 4-nitro-o-aniline N- (2-methoxy-4-nitrophenyl) amide
H (II)H (II)
Ziskaná eloučenina se izoluje « potce hydrogenuje a mesylaci v aprotickém rozpouštěd le se převede na N'-(4-methaneulfonamido-2-i«ethoxyfenyl)amid N-fenylanthranilovó kyeeliny vzorce IZIThe resulting compound is isolated and hydrogenated and the mesylation in an aprotic solvent is converted to the N '- (4-methanesulfonamido-2-ethoxyphenyl) amide of the N-phenylanthranilylic acid of formula IZI
Ziskaná sloučenina ee izoluje a přečisti* načež se cyklizuje působeni» foeforoxychloridu na 4'-(9-akridinyla»ino)-3*-raethoxymethansulfonanilid· Surový produkt ee rozpustí ve eměei vodného roztoku hydroxidu alkalického kovu a s vodou misitelnáho organického rozpouštědla a poto» ee vyaráži působením vodného roztoku alkalického hydrogenuhličitanu a překrystaluje aa ze směsi dimethylacetemidu a vody* Získaný 4'-(9-akrldinylamino)-3'-methoxymethansulfonanllid se rozpuati v kyselině mléčné a působením s vodou míeitelného organického rozpouštědla* a výhodou dioxanu, tetrahydrofuranu, methanolu a ethanolu, se vysráži připravený laktát,The obtained compound is isolated and purified, whereupon cyclization of 4 '- (9-acridinyl-amino) -3 * -ethoxymethanesulfonanilide is cyclized by the action of phosphorus oxychloride. The crude product is dissolved in a mixture of aqueous alkali metal hydroxide solution and a water miscible organic solvent and The resulting 4 '- (9-acridinylamino) -3'-methoxymethanesulfonanilide is dissolved in lactic acid and treated with a water-miscible organic solvent *, preferably dioxane, tetrahydrofuran, methanol, and a mixture of dimethylacetemide and water. ethanol, precipitates the prepared lactate,
Oe výhodné/ jestliže se ve všech stupních syntézy jako aprotická rozpouštědlo použije benzen a toluen, Oe také výhodná, jestliže ee jako meeylačni činidlo použije chlorid methansulfonovó kyseliny a Jako organické rozpouštědlo misitelnó a vodou dioxan, dimethylacetamid,' ethanol, aceton a dimethylformamid*If benzene and toluene are used as aprotic solvents in all steps of the synthesis, it is also advantageous if methanesulfonic acid chloride is used as the mesylating agent and dioxane, dimethylacetamide, ethanol, acetone and dimethylformamide are miscible with water as an organic solvent.
Způeob podle vynálezu bude dále bliže objasněn v následujícím přikladu*The method according to the invention will be explained in more detail in the following example.
PřikladExample
149 g N-fenylanthranilové kyseliny a 77 «1 thionylchloridu v 700 ml bezvodého benzenu se míchá 15 minut při teplotě místnosti, načež ea rozpouštědlo a přebytek thionylchloridu odpaři ve vakuu· Ka zbytku sa přidá 700 ml petroletheru*1 eměs se michá a potom přefiltruje· Zbytek na filtru ae dvakrát promyje 100 ml petroletheru a spojené etherové filtráty ee odpeři ve vakuu· Ke zbytku ee přidá 1000 ml bezvodého benzenu a 235 g149 g of N-fenylanthranilové acid and 77 «1 thionyl chloride in 700 ml of anhydrous benzene was stirred for 15 minutes at room temperature EA solvent and excess thionyl chloride was evaporated in vacuo · Ka residue was added 700 ml of petroleum ether * 1 EMES was stirred, then filtered · The filter residue ae was washed twice with 100 ml of petroleum ether and the combined ether filtrates were evaporated in vacuo. To the residue ee was added 1000 ml of anhydrous benzene and 235 g.
4-nitro-o-anisidinu a zahřívá se 1*5 hodiny k varu· Hqrkó reakčni aměe ee přefiltruje a zbytek na filtru se dvakrát promyje 100 ml bezvodého benzenu· Ze spojených benzenových filtrátů se odpaři 800 al rozpouštědla·' potom se přidá 200 ml ethanolu a vyerážený produkt se přefiltruje a promyje třikrát 100 al ethanolu* Po vysušeni se získá 229 g žlutého produktu ve formě N*-(2-raethoxy-4-nitrofenyl)»amidu N-fenylanthranilové kyseliny s teplotou tání 141 až 142 °C, což představuje 90 % teoretického výtěžku·4-nitro-o-anisidine and heated to boiling for 1 * 5 hours. The reaction medium is filtered and the residue is washed twice with 100 ml of anhydrous benzene. 800 l of solvent are evaporated from the combined benzene filtrates. ethanol and the precipitated product is filtered and washed three times with 100 l of ethanol. After drying, 229 g of yellow product are obtained in the form of N * - (2-methoxyethoxy-4-nitrophenyl) -amide of N-phenylanthranilic acid, m.p. which represents 90% of the theoretical yield ·
218 g získaného N*-(2-methoxy-4-nitrofenyl)»amidu N-fenylanthranilové kyseliny ee přidá k 1500 ml benzenu e za neustálého míchání ee redukuje vodikem za použiti Raney niklu 2 hodiny· K reakčni směsi se přidá 300 g bezvodého síranu sodného a po třech hodinách se sušicí činidlo a katalyzátor odfiltrují* zbytek na filtru se třikrát promyje 200 ml benzenu* Spojený filtrát ee ve vakuu zahusti na objem 1000 ml, přidá se 53 ml bezvodého pyridinu a 51 ml chloridu methansulfonová kyseliny a tři hodiny se zahřívá k varu· Potom ee rozpouštědlo odpaří ve vakuu a zbytek se rozpustí v 1500 ml 4% hydroxidu sodného. Získaný roztok se přefiltruje e filtrát se pomalu vlije do intensivně míchané 7% kyseliny chlorovodíkové e ledem (1500 ml)* Vysrážený surový produkt se odfiltruje* třikrát promyje 200 ml destilované vody a překrystaluje z ethanolu, přičemž se ziská 210 g N'-(4-methansulfonamido-2-methoxyfenyl)amidu N-fenylanthranilové kyseliny o teplotou táni 141 až 142 °C»· což představuje 85 % teoretického výtěžku*218 g of the obtained N * - (2-methoxy-4-nitrophenyl) -amide of N-phenylanthranilic acid ee are added to 1500 ml of benzene e with stirring and ee reduced with hydrogen using Raney nickel for 2 hours. 300 g of anhydrous sulfate are added to the reaction mixture. The combined filtrate was concentrated in vacuo to a volume of 1000 ml, 53 ml of anhydrous pyridine and 51 ml of methanesulfonic acid chloride were added and the mixture was heated for 3 hours. The solvent is then evaporated off under vacuum and the residue is dissolved in 1500 ml of 4% sodium hydroxide. The solution obtained is filtered and the filtrate is poured slowly into intensively stirred 7% hydrochloric acid in ice (1500 ml). The precipitated crude product is filtered off * washed three times with 200 ml of distilled water and recrystallized from ethanol to give 210 g of N '- -methanesulfonamido-2-methoxyphenyl) N-phenylanthranilic acid amide having a melting point of 141-142 ° C », which represents 85% of the theoretical yield *
206 g získaného N'-(4-methensulfonamido-2-methoxyfenyl)amidu N-fenylanthranilové kyseliny ββ přidá k 300 ml fosforoxychloridu a zahřívá se k varu pod zpětným chladičem jednu hodinu. Potom se fosforoxychlorid oddestiluje ve.vakuu,; ke zbytku se přidá 300 ml díoxanu e přefiltruje. Získaný produkt ee třikrát promyje 100 ml dioxenu. Zbytek na fil_ tru se rozpustí ve směsi 2500 ml 4% vodného roztoku hydroxidu sodného a 500 ml dioxanu* získaný roztok ae přefiltruje a filtrát ee pomalu za intenzivního mícháni přidává do 3000 al 8% vodného roztoku hydrogenuhličitanu sodného. Vysrážený produkt ee odfiltruje, třikrát promyje 250 ml destilované vody a rozpustí v 750 ml teplého dimethylacetamidu. Získaný roztok se přefiltruje, filtrát se zehřeje na 90 °C a za intenzivního mícháni ee přidá 1200 ml destilované vody 80 °C teplé. Směs,' ze které produkt začiná krystalovat, se pomalu ochladí na teplotu místnosti, přefiltruje a zbytek na filtru se třikrát promyje 100 ml methanolu. Po vysušeni se ziská 169 g 4’-(9-akrldinylamino}-3'- methoxymethansulfonanilidu teploty táni 232 až 233 °C,· což představuje 86 % teoretického výtěžku.206 g of the obtained N-phenylanthranilic acid N '- (4-methanesulfonamido-2-methoxyphenyl) amide ββ are added to 300 ml of phosphorus oxychloride and heated under reflux for one hour. The phosphorus oxychloride is then distilled off under vacuum. 300 ml of dioxane are added to the residue and filtered. The product obtained was washed three times with 100 ml of dioxene. The residue on the filter was dissolved in a mixture of 2500 ml of 4% aqueous sodium hydroxide solution and 500 ml of dioxane * and the resulting solution was filtered and the filtrate was slowly added with vigorous stirring to 3000 and 8% aqueous sodium bicarbonate. The precipitated product is filtered off, washed three times with 250 ml of distilled water and dissolved in 750 ml of warm dimethylacetamide. The solution obtained is filtered, the filtrate is heated to 90 ° C and, with vigorous stirring, 1200 ml of distilled water 80 ° C are added. The mixture from which the product starts to crystallize is slowly cooled to room temperature, filtered and the residue on the filter is washed three times with 100 ml of methanol. After drying, 169 g of 4 ' - (9-acridinylamino) -3 ' -methoxymethanesulfonanilide melting at 232 DEG -233 DEG C. is obtained, which represents 86% of the theoretical yield.
Analýza: pro C21H19N3°3S vypočteno 64,10 % C,' 4,-87 % H; nalezeno 64,-20 % C,· 4,-87 % HFor C 21 H 19 N 3 O 3 S requires C, 64.10%; H, -87%; Found: C, 64. -20%; H, 4.87%
64,22 5,-0264.22 5, -02
CS 272235 52CS 272235 52
NMR (CFgCOOH)» <5*3,3 (singlet, 3H/ CHgSOg-)/ 3,7 (einglet, 3H/ CHgO-)/ 7,0 - 8,2 (multiplat/ 11H/ aromáty),NMR (CF 3 COOH) <5 * 3.3 (singlet, 3 H / CH 3 SO 8 -) / 3.7 (einglet, 3 H / CH 3 O -) / 7.0-8.2 (multiplat / 11 H / aromatics),
IC (KBr): 3380 cm1/ 1340 cm1/ 990 cm’1.IR (KBr) 3380 cm -1 / 1340 cm 1/990 cm 1st
MS(FD)» 393MS (FD) > 393
15/7 g 4'-(9-akridinylamino)-3'-methoxymethanoulfonanllidu ae za mícháni rozpustí ve 40 ml 40% kyseliny mléčná při 80 °C, K získanému roztoku ss po částech přidá 600 ml dioxanu, Z roztoku začne produkt krystalovat,po 1 hodině es mícháni přeruěí a roztok se nechá etát 10 hodin, Vysréžené látka se odfiltruje* promyje třemi dávkami vždy 50 ml dioxanu a vyeuěi, přičemž se ziská 17/6 g 4'-(9-akridinylemino)-3'-methoxymetheneulfonanilid-laktátu o teplotě táni 168 až 174 °C, což představuje 91 % teoretického výtěžku.15/7 g of 4 '- (9-acridinylamino) -3'-methoxymethanoulphonanilide are dissolved in 40 ml of 40% lactic acid at 80 ° C with stirring. 600 ml of dioxane are added in portions to the obtained solution. After stirring for 1 hour, the solution is discontinued and the solution is left to stand for 10 hours. The precipitated substance is filtered off, washed with three portions of 50 ml each of dioxane and dried to give 17/6 g of 4 '- (9-acridinyl) amino. lactate, m.p. 168-174 ° C, representing 91% of the theoretical yield.
Analýza» pro C24H25N3°6S vypočteno 59/61 % C/ 5/21 % H, 8,69 % Ν» nalezeno 59/41 % C/ 5/26 % H, 8,39 % N,For C 24 H 25 N 3 ° 6 S calculated 59/61% C / 5/21% H, 8.69% Ν »found 59/41% C / 5/26% H, 8.39% N,
NMR (DMSO)» <f 1/2 dublet, 3H(CHg-kyseliny)» 3,0 singlet, 3H (CHgSOg-)» 3,6 einglet, 3H (CHgO-)} 4/1 kvartet, 1H, (-CH-OH)j 6,7 - 8,0/ multiplst, 11H (aromáty),NMR (DMSO) <f 1/2 doublet, 3H (CHg-acids) 3,0 3.0 singlet, 3H (CHgSOg-) 3,6 3.6 einglet, 3H (CHgO-)} 4/1 quartet, 1H, (- CH-OH) 6.7 - 8.0 / multipl, 11H (aromatics),
IC (KBr)» 1620 cm1/ 1530 cm1, 1340 cm1, 1160 cm’1/, 995 cm1.IR (KBr) »1 1620 cm / 1530 cm 1, 1340 cm 1, 1160 cm-1 /, 995 cm 1st
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL27153688A PL271536A1 (en) | 1988-03-30 | 1988-03-30 | Method of obtaining 4'-/9-acrydinylamine/-3'-methoxymethanesulfonoanilide lactate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS356788A2 CS356788A2 (en) | 1990-03-14 |
| CS272236B2 true CS272236B2 (en) | 1991-01-15 |
Family
ID=20041360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS883567A CS272236B2 (en) | 1988-03-30 | 1988-05-25 | Method of -/9-acrydinylamino)-methoxymethanesulphonanilide production |
Country Status (5)
| Country | Link |
|---|---|
| CS (1) | CS272236B2 (en) |
| DD (1) | DD272646A5 (en) |
| HU (1) | HU201019B (en) |
| PL (1) | PL271536A1 (en) |
| SU (1) | SU1605923A3 (en) |
-
1988
- 1988-03-30 PL PL27153688A patent/PL271536A1/en unknown
- 1988-05-25 CS CS883567A patent/CS272236B2/en unknown
- 1988-05-27 SU SU884355825A patent/SU1605923A3/en active
- 1988-06-08 HU HU882964A patent/HU201019B/en not_active IP Right Cessation
- 1988-06-09 DD DD88316596A patent/DD272646A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HU201019B (en) | 1990-09-28 |
| PL271536A1 (en) | 1989-10-02 |
| SU1605923A3 (en) | 1990-11-07 |
| CS356788A2 (en) | 1990-03-14 |
| HUT50129A (en) | 1989-12-28 |
| DD272646A5 (en) | 1989-10-18 |
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