Synthetic method of capecitabine intermediate 5-deoxy-D-ribofuranose

A technology of ribofuranose and capecitabine, which is applied in the directions of deoxy/unsaturated sugars, chemical instruments and methods, sugar derivatives, etc., can solve the problem of high cost, and achieve low synthesis cost, simple post-processing and high yield. Effect

Inactive Publication Date: 2010-09-29
河南省健康伟业生物医药研究股份有限公司
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  • Abstract
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  • Application Information

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Problems solved by technology

[0005] The annual sales of capecitabine in the current domestic market has reached 1 billion yuan, and it is still growing. It ranks second among metabolic cancer treatment drugs, but the cost of capecitabine has always been high. Many cancer patients reduce the burden and bring good news. Its synthetic route has been paid attention to by many scientific researchers. In order to further innovate and transform the synthetic route of capecitabine, greatly reduce its synthetic cost, and develop new technical methods to Improve the synthesis yield of capecitabine intermediates, greatly reduce the cost, and have important application value and industrialization value

Method used

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  • Synthetic method of capecitabine intermediate 5-deoxy-D-ribofuranose

Examples

Experimental program
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Embodiment 1

[0020] Example 1 Preparation of 1-methyl-2,3-O-isopropylidene-D-ribofuranose with D-ribose as raw material

[0021] Add 50g of D-ribose (0.33mol) to a mixed solvent of 300ml of anhydrous acetone and 100ml of anhydrous methanol, add 45ml of anhydrous zinc chloride (0.33mol) and 0.5ml of concentrated sulfuric acid, react at room temperature to 50°C for 24h, filter Finally, add 1mol / L sodium bicarbonate to the filtrate to neutralize the pH to 7.0, evaporate acetone and methanol under reduced pressure, then extract with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, filter, and evaporate the organic phase to dryness , to obtain 62.0 g (0.30 mol) of light yellow liquid 1-methyl-2,3-O-isopropylidene-D-ribofuranose, with a yield of 92%.

[0022] 1 H NMR ((CD 3 ) 2 SO, 400MHz): δ5.41(d, 1H, 1-H), 4.65(m, 1H, 4-H), 4.53(m, 1H, 2-H), 4.23(m, 1H, 3-H) , 3.78(d, J=2.6Hz, 1H, 5-H), 3.52(d, J=2.6Hz, 1H, 5-H), 3.47(s, 3H, CH 3 ), 1.27 (s, 6H, CH 3 ); ESI MS (C 9 h...

Embodiment 2

[0023] Example 2 Using 1-methyl-2,3-O-isopropylidene-5-deoxy-D-ribofuranose as raw material to synthesize 5-deoxy-D-ribofuranose

[0024] Dissolve 50g of 1-methyl-2,3-O-isopropylidene-5-deoxy-D-ribofuranose (0.27mol) in water, add 30g of cationic resin, stir at room temperature for 24h, filter out the cationic resin after the reaction , and concentrated under reduced pressure to obtain 35.6 g (0.27 ml) of light yellow viscous liquid 5-deoxy-D-ribofuranose, with a yield of 99.9%.

[0025] 1 H NMR ((CD 3 ) 2 SO, 400MHz): δ5.57(d, 1H, 1-H), 4.53(m, 1H, 3-H), 4.01(m, 1H, 4-H), 3.72(m, 1H, 3-H) , 1.17(d, J=3.6Hz 3H, CH 3 ); ESI MS (C 5 h 10 o 4 ): 135.7 (MH + ).

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Abstract

The invention belongs to the technical field of medicinal chemistry and discloses a preparation method of capecitabine intermediate 5-deoxy-D-ribofuranose, which comprises the steps of taking D-ribose as a raw material, carrying out protection and deprotection, reducing and synthesizing the 5-deoxy-D-ribofuranose. The method has the advantages of high yield, simple operation, mild conditions, no pollution and high economic benefits, and can realize the industrial production. The synthesis of capecitabine through the method can improve the yield by more than 30% and reduce the cost by more than 30%, thereby greatly reducing the economic burden on patients with cancers.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of a capecitabine intermediate, that is, a synthesis method of the capecitabine intermediate 5-deoxy-D-ribofuranose. Background technique [0002] Capecitabine (structural formula 1) was developed by the Swiss pharmaceutical company Roche (Roche), and was marketed in the United States, Canada, Sweden and other countries under the trade name Xeloda in 1998. At present, my country has approved the import of this product, which is clinically used in the treatment of advanced breast cancer, colorectal cancer and other solid tumors. Xeloda has fewer side effects, and the general side effects often include fatigue, but severe cases are rare. Other common side effects were mucositis, fever, weakness, lethargy, etc., but none of them were serious. [0003] [0004] Structural formula 1 The chemical structural formula of capecitabine [0...

Claims

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Application Information

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IPC IPC(8): C07H3/08C07H1/00
Inventor张红雨叶乾堂于振艳陈蕴
Owner河南省健康伟业生物医药研究股份有限公司