158798-73-3

Usage

Originator

Xeloda,Hoffmann - La Roche Inc.,USA

Therapeutic Function

Antitumor

InChI:InChI=1/C9H12FN3O4/c1-3-5(14)6(15)8(17-3)13-2-4(10)7(11)12-9(13)16/h2-3,5-6,8,14-15H,1H3,(H2,11,12,16)/t3-,5-,6-,8-/m1/s1

Upstream product

• 161599-46-8 (2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate 
• 862508-03-0 (5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid amyl ester 
• 1071455-34-9 pentyl (5-fluoro-2-((trimethylsilyl)oxy)pyrimidin-4-yl)carbamate 
• 638-41-5 pentyl chloroformate 
• 27821-07-4 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose 
• 4137-56-8 methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside 
• 23202-81-5 methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside 
• 279673-09-5 (2R,3R,4S,5R)-5-methyltetrahydrofuran-2,3,4-triol 
• 36468-53-8 β-D-ribofuranose 
• 4099-85-8 ((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 50610-99-6 1-O-methyl-2,3-O-isopropylidene-5-O-(methanesulfonyl)-β-D-ribofuranoside 
• 41864-22-6 1,1'-Carbonyl-di-(1,2,4-triazole) 
• 2022-85-7 Flucytosine 
• 71-41-0 pentan-1-ol 

Downstream Products

• 66335-38-4 5'-deoxy-5-fluorocytidine 

Relevant academic research and scientific papers

Preparation of capecitabine intermediate

The invention belongs to the field of medicine synthesis, and provides a preparation method of capecitabine intermediate, in particular to a compound of the formula I II in the presence of a ketone solvent and an organic base.

Capecitabine intermediate

The invention belongs to the field of medicine synthesis, and discloses a capecitabine intermediate (V) and a preparation method thereof. The preparation method comprises the step of under the actionof a catalyst, enabling derivatives (III) of 5-deoxy-D-ribose of which 2,3-hydroxyl is protected with Fmoc- and activated 5-flucytosine (IV) to be coupled to obtain the capecitabine intermediate (V).The method is simple and easy to operate, simple in post-treatment, high in product purity and suitable for industrial production.

Cytidine derivative and method for preparing capecitabine medicines through derivative

The invention discloses a 5-deoxy-D-ribofuranose 1-[2-(1-styyl) benzoate] derivative as shown in a general formula (I) and a preparation method of the derivative, and a method for preparing a N4-deoxycarbonyl cytidine derivative and antitumor medicines namely capecitabine by using the general formula (I) as a raw material, wherein the structure of the general formula (I) is as shown in the description. The 5-deoxy-D-ribofuranose 1-[2-(1-styyl) benzoate] derivative as the raw material of a reaction is used as a glycosyl donor and can be activated under the condition of Lewis acid trimethylsilyl trifluoromethanesulfonate and N-lodosuccinimide in catalysis quantity, so that Lewis acid in traditional use equivalent or excessive quantity is avoided, and a reaction system is mild, free from occurrence of other side reactions and efficient.

Continuous-Flow Sequential Schotten-Baumann Carbamoylation and Acetate Hydrolysis in the Synthesis of Capecitabine

Capecitabine is an important anticancer drug whose synthesis comprises late-stage carbamoylation and ester hydrolysis. Herein we report the use of the Schotten-Baumann reaction in order to perform these transformation in one pot both in batch and under continuous flow. In batch, capecitabine was obtained in 82% yield in 5 h, while under continuous flow it was obtained in 81% yield in 30 min. This one-pot reaction reduces the chemical waste produced, labor, time, and cost and additionally comprises the use of environmentally friendly solvents and reagents as well as energy-efficient and safe methods, all of which fulfill the requirements of a green process.

A capecitabine synthetic method

The invention belongs to the technical field of medicine preparation and relates to a synthetic method of capecitabine. The method comprises the following steps: 1) condensation reaction: reacting 2', 3'-bi-O-acetyl-5'-deoxy-5-fluoro-cytidine with halo n-amyl formate in the presence of an acid applying agent and a dimethylamino-pyridine catalyst to prepare N-pentyloxy carbonyl-2' 3'-bi-O-actyl-5'-deoxy-5-fluoro-cytidine; and 2) hydrolysis reaction: carrying out hydrolysis reaction on N-pentyloxy carbonyl-2' 3'-bi-O-actyl-5'-deoxy-5-fluoro-cytidine in the presence of an inorganic base to prepare the final product capecitabine. Compared with the prior art, the method provided by the invention has the advantages that by taking the inorganic base as the acid applying agent, use of a lot of organic bases is avoided and therefore the yield is improved, the production cost lowered, the environmental pollution is reduced, the physical health of the worker is ensured, and industrial production is facilitated.

Method for preparing capecitabine from capecitabine waste water extract

The invention discloses a method for preparing capecitabine from capecitabine waste water extract. The method comprises the following steps: extracting 5'-deoxy-5-gemcitabine from capecitabine waste water, introducing isopropylidene at hydroxy of a saccharide structure part of a compound for protection, further introducing acryl at an amino group, and eliminating the isopropylidene protection from the saccharide structure part to obtain capecitabine. By adopting the method, not only is the waste water harmlessly treated, but also the reutilization of impurities in the waste water is realized, the production cost is decreased, the operation is convenient, raw materials needed for preparation are easy to obtain, and the industrialized production is facilitated (shown in the description).

A capecitabine synthetic method

The invention discloses a synthesis method for capecitabine. The method comprises the following five steps of (1) carrying out reaction on D-ribose and acetic anhydride so as to prepare a compound V; (2) carrying out reaction on the compound V and 5-FC so as to prepare a compound IV; (3) hydrolyzing the compound IV so as to prepare a compound III; (4) hydroxylating the compound III so as to prepare a compound II; and (5) deprotecting so as to prepare the capecitabine (a compound I) finally. The synthesis method has simple operation steps and mild reaction conditions, is easy to extract and separate the product, has high yield, greatly lowers the production cost, and is beneficial to industrial production.

Preparation method of 2'-3'-bis-O-acetyl-5'-deoxy-5-fluoro-N4-[(pentyloxy)carbonyl]cytidine

The invention relates to the field of pharmaceutical chemistry, in particular to a preparation method of 2'-3'-bis-O-acetyl-5'-deoxy-5-fluoro-N4-[(pentyloxy)carbonyl]cytidine; the method comprises: reacting a compound of formula IV as a raw material with n-amyl chloroformate under the action of K3PO4 to obtain the compound of formula V, 2',3'-bis-O-acetyl-5'-deoxy-5-fluorine-N4-[(pentyloxy)carbonyl]cytidine. The invention also provides application of the method in the preparation of capecitabine. The preparation method has the advantages that reaction yield can be significantly increased, product purity is high, reaction conditions are mild, the use of pyridine is avoided, pyridine residue in the product is avoided, and the method is suitable for industrial production of medicine.

For a continuously operated synthetic capecitabine method

The invention discloses a method for synthesizing capecitabine by continuous operations. The method comprises the following steps: acylating 5'-deoxy-2', 3'-2-O-acetyl-5-gemcitabine to obtain 5'-deoxy-2',3'-2-O-acetyl-N-[(pentyl acetal) carbonyl]-5-fluorine cytidine methylene chloride solution; then directly adding an alkaline aqueous solution; adding alcohol, and hydrolyzing and synthesizing capecitabine. The method disclosed by the invention is short in reaction time to more than ten minutes, fewer in treatment steps, simple to operate, low in cost and small in pollution.

Preparation method of capecitabine

The invention belongs to the field of medicinal chemistry and specifically relates to a preparation method of capecitabine. Firstly, steps of silylanization, glycosylation, acylation, esterification and deprotection are successively carried out. An intermediate doesn't require separation and purification, and a product is synthesized by a one-pot method. The final product capecitabine is separated and purified through extraction and recrystallization. The reaction operation is simple. Secondly, during the glycosylation reaction, BF3.OEt2 is used as a Lewis acid, production cost is low, and reaction materials have little toxicity. Thirdly, during the silylanization reaction, trimethylchlorosilane is used as a silylating reagent, dichloromethane is used as a solvent, potassium carbonate is used as an acid-binding agent, and the agents are easy to remove after the end of the reaction, which is beneficial to the next reaction. In addition, reaction temperatures of the reaction steps of silylanization, glycosylation, acylation and esterification in the preparation method are all 20-30 DEG C, and reaction conditions are mild.