CS264454B1 - 2-deoxy-5,6-dihydro-5-azacytidine and process for preparing thereof - Google Patents
2-deoxy-5,6-dihydro-5-azacytidine and process for preparing thereof Download PDFInfo
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- CS264454B1 CS264454B1 CS876304A CS630487A CS264454B1 CS 264454 B1 CS264454 B1 CS 264454B1 CS 876304 A CS876304 A CS 876304A CS 630487 A CS630487 A CS 630487A CS 264454 B1 CS264454 B1 CS 264454B1
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- azacytidine
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- 238000004519 manufacturing process Methods 0.000 title abstract 2
- LAOLDMMWVYDDID-KVQBGUIXSA-N 6-amino-3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,4-dihydro-1,3,5-triazin-2-one Chemical compound C1NC(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 LAOLDMMWVYDDID-KVQBGUIXSA-N 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 150000007522 mineralic acids Chemical class 0.000 claims description 10
- 150000007524 organic acids Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229960002756 azacitidine Drugs 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000006136 alcoholysis reaction Methods 0.000 claims description 3
- -1 alkali metal alkoxide Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 2
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 claims 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- RFYOMFHIKWGPEC-RRKCRQDMSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,3,5-triazinane-2,4-dione Chemical compound O=C1NC(=O)N(C)CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 RFYOMFHIKWGPEC-RRKCRQDMSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- RFYOMFHIKWGPEC-UHFFFAOYSA-N 5,6-Dihydro-5-azathymidine Natural products O=C1NC(=O)N(C)CN1C1OC(CO)C(O)C1 RFYOMFHIKWGPEC-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001304058 Streptomyces platensis subsp. clarensis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
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- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Řešení se týká nového 2'-deoxy-5,, 6- -dihydro-5-azacytidinu a způsobu jeho výroby. Látku lze využít ve farmaceutickém průmyslu.The solution relates to the new 2'-deoxy-5, 6- -dihydro-5-azacytidine and its method production. The substance can be used in a pharmaceutical industry.
Description
Vynález se týkáThe invention relates
2'-deoxy-5,6-dihydro-5-azacytidinu vzorce2'-deoxy-5,6-dihydro-5-azacytidine of formula
a jeho adičních solí s netoxickými anorganickými Či organickými kyselinami. Předmětem předloženého vynálezu je také způsob přípravy 2'-deoxy-5,6-dihydro-5-azacytidinu vzorce I, který je novým analogem 2'-deoxycytidinu a jeho adičních solí s uvedenými kyselinami.and its addition salts with non-toxic inorganic or organic acids. The present invention also provides a process for the preparation of 2'-deoxy-5,6-dihydro-5-azacytidine of formula I which is a novel analog of 2'-deoxycytidine and its addition salts with said acids.
2'-deoxy-5,6-dihydro-5-azacytidin vzorce I je novým analogem 2'-deoxyoytidinu, od něhož se dá formálně odvodit záměnou skupiny CH v poloze 5 pyrimidinového jádra isoelektronic kýn atomem dusíku a následnou adicí vodíku na dvojnou vazbu v poloze 5,6 triazinového kruhu. 2-deoxy-5,6-dihydro-5-azacytidin vzorce I se řadí do skupiny 5,6-dihydroderivátů 2'-deoxy-5-azapyrimidinových nukleosidů. Nejvýznamnější látkou z této skupiny je nukleosidové antibiotikum 5,6-dihydro-5-azathymidin (DHAdT), které bylo isolováno z filtrátů kultury S. platensis var. clarensis ^DeBoer, Bannister: USA pat. 3 907 643 (1975)) a vykazuje účinnost proti DNA virům a gram-negativním bakteriím. Očinek DHAdT je revertován thymidinem, 2*-deoxyuridinem a 2'-deoxycytidinem. Z uvedených důvodů lze antivirálni, případně antibakteriální účinnost očekávat také u 2'-deoxy-5,6-dihydro-5-azaoytidinu vzorce I. Dihydronukleosid vzorce I je na rozdíl od 2'-deoxy-5-azacytidinu stálý ve vodných roztocích v širokém rozmezí pH a je také podstatně lépe rozpustný ve vodě.The 2'-deoxy-5,6-dihydro-5-azacytidine of formula I is a novel analog of 2'-deoxyoytidine from which it can be formally derived by substituting the CH group at the 5-position of the pyrimidine nucleus with an nitrogen atom and subsequently adding hydrogen to the double bond in the position 5,6 of the triazine ring. The 2-deoxy-5,6-dihydro-5-azacytidine of the formula I belongs to the group of 5,6-dihydroderivatives of 2'-deoxy-5-azapyrimidine nucleosides. The most prominent of this group is the nucleoside antibiotic 5,6-dihydro-5-azathymidine (DHAdT), which was isolated from culture filtrates of S. platensis var. clarensis ^ DeBoer, Bannister: U.S. Pat. No. 3,907,643 (1975)) and shows activity against DNA viruses and gram-negative bacteria. The effect of DHAdT is reversed by thymidine, 2'-deoxyuridine and 2'-deoxycytidine. For this reason, 2'-deoxy-5,6-dihydro-5-azaoytidine (I) can also be expected to have antiviral or antibacterial activity. pH range and is also substantially better soluble in water.
Způsob výroby 2'-deoxy-5,6-dihydro-5-azacytidinu vzorce I spočívá v tom, že se volný nebo blokovaný 2'-deoxy-5-azacytidin obecného vzorce IIThe process for the preparation of 2'-deoxy-5,6-dihydro-5-azacytidine of formula I is characterized in that the free or blocked 2'-deoxy-5-azacytidine of formula II
(II) ,(II),
ROCH,ROCH,
RO kde R je vodík nebo acyl, redukuje práškovým zinkem v bezvodé karboxylové kyselině s 1 až 4 atomy uhlíku a v případě použití sloučeniny vzorce II, kde R je acyl, se vzniklý 2'-deoxy-3',5'-di-0-acyl-5,6-dihydro-5-azacytidin obecného vzorce IIIWhere R is hydrogen or acyl, it is reduced by zinc powder in anhydrous carboxylic acid having 1 to 4 carbon atoms, and when a compound of formula II wherein R is acyl is used, 2'-deoxy-3 ', 5'-di-O is formed -acyl-5,6-dihydro-5-azacytidine of formula III
RO kde R je acyl, případně jeho adiční sůl s organickou či anorganickou kyselinou, podrobí alkoholyse a získaný 2*-deoxy-5,6-dihydro-5-azacyt.idin vzorce I se v případě potřeby převede na adiční sůl s netoxickou anorganickou či organickou kyselinou.Where R is acyl, or an organic or inorganic acid addition salt thereof, is subjected to an alcoholic reaction and the resulting 2'-deoxy-5,6-dihydro-5-azacytidine of formula I is converted, if necessary, to a non-toxic inorganic or organic acid.
Redukce probíhá velmi dobře již při teplotě místnosti za použití pěti až desetinásobku teoretického množství práškového zinku. Jako karboxylová kyselina se osvědčila komerčně dobře dostupná kyselina octová. Redukci méně stabilního blokovaného 2'-deoxy-5-azacytidinu je vhodné provádět ve směsi karboxylové kyseliny a 2,2-dimethoxypropanu, který zaručuje bezvodost reakčního prostředí. Isolace volného dihydroderivátu vzorce I se provádí s výhodou ionexovou technikou. Blokovaný nukleosid vzorce III se isoluje s výhodou vytřepáním do chloroformu a převedením na adiční sůl s organickou či anorganickou kyselinou. Alkoholýza 2'-deoxy-3,5'-tri-0-acyl-5,6-dihydro-5-azacytidinu vzorce III, případně jeho adiční solí s anorganickou či organickou kyselinou, se provádí roztokem alkoxidu alkalického kovu v alkanolu s 1 až 4 atomy uhlíku, s výhodou methoxidem sodným v methanolu.The reduction proceeds very well already at room temperature using five to ten times the theoretical amount of zinc powder. Commercially available acetic acid has proved to be a carboxylic acid. The reduction of the less stable blocked 2'-deoxy-5-azacytidine is desirably carried out in a mixture of carboxylic acid and 2,2-dimethoxypropane, which guarantees the anhydrous nature of the reaction medium. The isolation of the free dihydroderivative of formula (I) is preferably carried out by an ion exchange technique. The blocked nucleoside of formula III is preferably isolated by shaking it into chloroform and converting it into an organic or inorganic acid addition salt. The alcoholysis of the 2'-deoxy-3,5'-tri-O-acyl-5,6-dihydro-5-azacytidine of formula III, or its addition salt with an inorganic or organic acid, is carried out with a solution of an alkali metal alkoxide in an 4 carbon atoms, preferably sodium methoxide in methanol.
V dalším je vynález blíže objasněn v příkladech provedení, aniž se na tyto jakkoliv omezuje.The invention is further illustrated by the following non-limiting examples.
Příklad 1Example 1
Příprava acetátu 2*-deoxy-5,6-díhydro-3',5'-di-0-p-toluoyl-5-azacytidinuPreparation of 2'-deoxy-5,6-dihydro-3 ', 5'-di-O-p-toluoyl-5-azacytidine acetate
Směs kyseliny octové (5 ml) a 2,2-dimethoxypropanu (2 ml) se ponechá 24 hodin stát při teplotě místnosti v uzavřené baňce. Pak se přidá postupně práškový zinek (0,65 g) a 2'-deoxy-3',5'-di-0-p-toluoyl-5-azacytidin (0,465 g; 1 mmol). Směs se 2,5 hodiny intensivně magneticky míchá při teplotě místnosti a nerozpustný materiál se odsaje přes fritu. Materiál na fritě se promyje postupně kyselinou octovou, methanolem a bohatě směsí chloroform-methanol' (9:1). Spojené filtráty se vytřepou vodou a 5% roztokem kyselého uhličitanu sodného. Organická vrstva se po vysušení (MgSO^) a přidáni kyseliny octové (0,1 ml) odpaří ve vakuu. Krystalizací zbytku ze směsi methanol-petrolether se získá po zpracování matečných louhů celkem 0,401 g (76 %) acetátu 2'-deoxy-5,6-dihydro-3',5'-di-0-p-toluoyl-5~azacytidinuí t.t. 142 až 146 °C (rozklad).A mixture of acetic acid (5 mL) and 2,2-dimethoxypropane (2 mL) was allowed to stand at room temperature in a sealed flask for 24 hours. Then zinc powder (0.65 g) and 2'-deoxy-3 ', 5'-di-O-p-toluoyl-5-azacytidine (0.465 g; 1 mmol) were added sequentially. The mixture was vigorously magnetically stirred at room temperature for 2.5 hours and the insoluble material was filtered off with suction through a frit. The frit material was washed sequentially with acetic acid, methanol and richly chloroform-methanol (9: 1). The combined filtrates were shaken with water and 5% sodium bicarbonate solution. After drying (MgSO4) and addition of acetic acid (0.1 mL), the organic layer was evaporated in vacuo. Crystallization of the residue from methanol-petroleum ether yielded a total of 0.401 g (76%) of 2'-deoxy-5,6-dihydro-3 ', 5'-di-O-p-toluoyl-5-azacytidine acetate m.p. M.p. 142-146 ° C (dec.).
Příklad 2Example 2
Příprava 2'-deoxy-5,6-dihydro-5-azacytidinuPreparation of 2'-deoxy-5,6-dihydro-5-azacytidine
Směs acetátu 2'-deoxy-5,6-3ihydro-3',5'-di-0-p-toluoyl-5-azacytidinu (0,527 g; 1 mmol), methanolu (6 ml) a methanolického !M-NaOCH3 (2 ml) se 24 hodin magneticky míchá při teplotě místnosti. Směs se okyselí kyselinou octovou (0,2 ml) a odpaří ve vakuu. Zbytek se promyje petroletherem a rozpustí ve vodě. Roztok surového produktu se nanese na sloupec silně kyselého katexu v NH^ + formě (20 ml) a sloupec se promyje vodou (300 ml). Produkt se ze sloupce vymyje ÍM-NH^OH (150 ml) a eluát se odpaří ve vakuu. Krystalizací zbytku z methanolu se po zpracování matečných louhů celkem ziská 0,193 g (84 2'-deody-5,6-dihydro-5-azacytidinu, t.t. 195 až 196 °C (rozklad).A mixture of 2'-deoxy-5,6-3-dihydro-3 ', 5'-di-O-p-toluoyl-5-azacytidine acetate (0.527 g; 1 mmol), methanol (6 mL) and methanolic 1 M-NaOCH 3 (2 mL) was stirred magnetically at room temperature for 24 hours. The mixture was acidified with acetic acid (0.2 mL) and evaporated in vacuo. The residue was washed with petroleum ether and dissolved in water. The crude product solution was applied to a strongly acidic cation exchange column in NH4 + form (20 mL) and the column was washed with water (300 mL). The product was eluted from the column with 1 H-NH 4 OH (150 mL) and the eluate was evaporated in vacuo. Crystallization of the residue from methanol gave a total of 0.193 g (84 2'-deody-5,6-dihydro-5-azacytidine, mp 195-196 ° C (dec.)) After mother liquor treatment.
Příklad 3Example 3
Směs 2'-deoxy-5-azacytidinu (0,338 g; 1 mmol), kyseliny octové (5 ml) a práškového zinku (0,65 g) se 24 hodin magneticky míchá při teplotě místnosti. Nerozpustný podíl se odsaje a promyje postupně kyselinou octovou a bohatě methanolem. Spojené filtráty se odpaří ve vakuu, zbytek se rozpustí ve vodě a roztok nanese na sloupec silně kyselého katexu v ŇH4 + formě (20 ml) a sloupec se promyje vodou (300 ml). Produkt se vymyje ÍM-NH^OH (150 ml) a eluát odpaří ve vakuu. Krystalizací zbytku z methanolu se získá po zpracování matečných louhů celkem 0,189 g (82 %) 2'-deoxy-5,6-dihydro-5-azacytidinuí t.t. 195 až 196 °C (rozklad).A mixture of 2'-deoxy-5-azacytidine (0.338 g; 1 mmol), acetic acid (5 mL) and zinc powder (0.65 g) was magnetically stirred at room temperature for 24 hours. The insoluble material is filtered off with suction and washed successively with acetic acid and rich methanol. The combined filtrates were evaporated in vacuo, the residue was dissolved in water, and the solution was applied to a strongly acidic cation exchange column in NH 4 + form (20 mL) and the column was washed with water (300 mL). The product was washed with 1 N-NH 4 OH (150 mL) and the eluate evaporated in vacuo. Crystallization of the residue from methanol gave a total of 0.189 g (82%) of 2'-deoxy-5,6-dihydro-5-azacytidine, m.p. 195-196 ° C (decomposition) after mother liquor treatment.
Příklad 4Example 4
Příprava acetátu 2'-deox.y-5,6-dihydro~5-azacytidinuPreparation of 2'-deoxyl-5,6-dihydro-5-azacytidine acetate
Roztok 2'-deoxy-5,6-dihydro-5-azacytidinu (0,230 g; 1 mmol) v methanolu se neutralizuje kyselinou octovou (0,06 gj 1 mmol). Směs se odpaří ve vakuu a zbytek krystaluje z methanolu Po zpracování matečných louhů se celkem získá 0,261 g (90 %) acetátu 2'-deoxy-5,6-dihydro-5-azacytidinu; t.t. 152 až 158 °C (rozklad).A solution of 2'-deoxy-5,6-dihydro-5-azacytidine (0.230 g; 1 mmol) in methanol was neutralized with acetic acid (0.06 g, 1 mmol). The mixture was evaporated in vacuo and the residue crystallized from methanol. After treatment of the mother liquors, a total of 0.261 g (90%) of 2'-deoxy-5,6-dihydro-5-azacytidine acetate was obtained; m.p. Mp 152-158 ° C (dec.).
Claims (5)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS876304A CS264454B1 (en) | 1987-08-28 | 1987-08-28 | 2-deoxy-5,6-dihydro-5-azacytidine and process for preparing thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS876304A CS264454B1 (en) | 1987-08-28 | 1987-08-28 | 2-deoxy-5,6-dihydro-5-azacytidine and process for preparing thereof |
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| CS630487A1 CS630487A1 (en) | 1988-10-14 |
| CS264454B1 true CS264454B1 (en) | 1989-08-14 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS876304A CS264454B1 (en) | 1987-08-28 | 1987-08-28 | 2-deoxy-5,6-dihydro-5-azacytidine and process for preparing thereof |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS264454B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1635836A4 (en) * | 2003-06-20 | 2008-09-10 | Koronis Pharmaceuticals Inc | Prodrugs of heteroaryl compounds |
| US8158605B2 (en) | 2007-09-26 | 2012-04-17 | Mount Sinai School Of Medicine | Azacytidine analogues and uses thereof |
-
1987
- 1987-08-28 CS CS876304A patent/CS264454B1/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1635836A4 (en) * | 2003-06-20 | 2008-09-10 | Koronis Pharmaceuticals Inc | Prodrugs of heteroaryl compounds |
| US8158605B2 (en) | 2007-09-26 | 2012-04-17 | Mount Sinai School Of Medicine | Azacytidine analogues and uses thereof |
| US8399420B2 (en) | 2007-09-26 | 2013-03-19 | Mount Sanai School of Medicine | Azacytidine analogues and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CS630487A1 (en) | 1988-10-14 |
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