- Preparation method for high-yield capecitabine impurity F
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The invention relates to a preparation method for a high-yield capecitabine impurity F. The preparation method comprises the following steps that (a) 2-methyl-1-pentanol, tetrahydrofuran and triethylamine are added into a reaction vessel, after nitrogen replacement is carried out, cooling is carried out to reach the temperature of less than or equal to 0 DEG C, a triphosgene tetrahydrofuran solution is dropwise added, heating is carried out for reaction, filtering is carried out so as to obtain a filtrate, and spin-drying is carried out so as to obtain a first mixture; (b) potassium carbonate,2',3'-di-O-acetyl-5'-deoxy-5-fulurocytidine and acetone are added into another reaction vessel, after nitrogen replacement is carried out, an acetone solution of the first mixture is dropwise added for reaction, and filtering is carried out so as to obtain a reaction solution of a second mixture; and (c) the reaction solution of the second mixture is cooled to be less than or equal to -10 DEG C,the pH value is adjusted to be alkaline for reaction, then the pH value is adjusted to be neutral, the acetone is spin-dried, extraction is carried out on an aqueous phase multiple times by using ethyl acetate, organic phases are combined, drying is carried out, then spin-drying is carried out, and column chromatography is carried out. The product obtained through the method has the advantages ofbeing high in purity and high in yield.
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- Rapid preparation method of capecitabine impurity F
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The invention relates to a rapid preparation method of a capecitabine impurity F. The preparation method comprises the following steps: (a) adding 2-methyl-1-butanol, tetrahydrofuran, triethylamine and nanometer titania into a reaction container, performing nitrogen displacement, cooling to a temperature of less than or equal to 0 DEG C, dropwise adding a tetrahydrofuran solution of triphosgene, reacting under UV-irradiation, filtering to obtain filtrate, and performing spin drying so as to obtain a first mixture; (b) adding potassium carbonate, 2', 3'-bi-O-acetyl-5'-deoxo-5-fluorocytidine andacetone into another reaction container, dropwise adding an acetone solution of the first mixture to react after nitrogen displacement, and filtering to obtain a reaction solution of a second mixture; and (c) cooling the reaction solution of the second mixture to a temperature of less than or equal to 10 DEG C below zero, regulating the pH value to be alkaline, and reacting. Therefore, oxidationand acylation of the 2-methyl-1-butanol can be promoted, so that the reaction time is shortened on the premise of ensuring the purity, and the process steps are simplified.
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- Preparation method of capecitabine impurity F
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The invention relates to a preparation method of a capecitabine impurity F. The preparation method comprises the following steps: (a) adding 2-methyl-1-butanol, tetrahydrofuran, triethylamine, nanometer titania and nano-iron oxide into a reaction container, performing nitrogen displacement, cooling to a temperature of less than or equal to 0 DEG C, dropwise adding a tetrahydrofuran solution of triphosgene, reacting under UV-irradiation, filtering to obtain filtrate, and performing spin drying so as to obtain a first mixture; (b) adding potassium carbonate, 2', 3'-bi-O-acetyl-5'-deoxo-5-fluorocytidine and acetone into another reaction container, dropwise adding an acetone solution of the first mixture to react after nitrogen displacement, and filtering to obtain a reaction solution of a second mixture; and (c) cooling the reaction solution of the second mixture to a temperature of less than or equal to 10 DEG C below zero, regulating the pH value to be alkaline, and reacting. Therefore,the product purity is improved on the premise of shortening the reaction time, and the process steps are simplified.
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- Synthesis and biological activity evaluation of cytidine-5′-deoxy-5- fluoro-N-[(alkoxy/aryloxy)] carbonyl-cyclic 2′,3′-carbonates
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Capecitabine, an oral prodrug of 5-FU was developed to improve the tumor selectivity and tolerability. To enhance the efficacy of capacitabine, a series of 5′-deoxy-5-fluorocytidine derivatives 5a-e were synthesized. In the present study, we investigated antitumor activity of 5′-deoxy-5- fluorocytidine derivatives both in vivo and in vitro methods. Title compounds were non-mutagenic to Salmonella typhimurium tester strain in Ames test. Compounds 5d and 5e are potent to inhibit the proliferation of NCI-69, PZ-HPV-7, MCF-7 and HeLa cells in MTT assay. In particular, 5d and 5e showed potent antitumor activities against L1210 leukemia cell line. Collectively, these findings suggest that 5d and 5e are more potent anti-cancer compounds than capecitabine.
- Jhansi Rani,Raghavendra,Kishore,Nanda Kumar,Hema Kumar,Jagadeeswarareddy
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p. 690 - 696
(2012/09/08)
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