Check patentability & draft patents in minutes with Patsnap Eureka AI!

Method for the preparation of 2'-deoxy-2',2'-difluoro cytidine

A technology of diflucytidine and nucleosides, applied in the field of stereoselective preparation of 2'-deoxy-2', which can solve the problems of low yield of β-anomer

Inactive Publication Date: 2007-08-01
HANMI SCI CO LTD
View PDF10 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method also yields only low yields of the β-anomer

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for the preparation of 2'-deoxy-2',2'-difluoro cytidine
  • Method for the preparation of 2'-deoxy-2',2'-difluoro cytidine
  • Method for the preparation of 2'-deoxy-2',2'-difluoro cytidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Example 1: 1-(2'-deoxy-2', 2'-difluoro-5-benzoyl-3-(4-phenyl)benzoyl-D-ribofuranosyl-4-aminopyrimidine- 2-keto

[0095]

Embodiment 1-1

[0097] 44.5g of cytosine, 252ml of hexamethyldisilazane and 252mg of ammonium sulfate were mixed and refluxed until the solution was uniform, and then refluxed for another hour. Thereto was added 200 ml of ethyl acetate and heated to remove remaining unreacted hexamethyldisilazane. To the resulting solution was added a mixture of 160 ml of heptane and 40 ml of diphenyl ether and 10.4 g of 1-α-bromo-2'-deoxy-2',2'-difluoro-D-ribofuranosyl- 5-Benzoyl-3-(4-phenyl)benzoate. The resulting mixture was allowed to react for 8 hours, while diphenyl ether (40ml) / heptane (4l) mixture was added dropwise thereto while distillation was carried out, and the reaction temperature was kept at 130-140°C. This step allows the continuous removal of bromotrimethylsilane from the reaction mixture during the course of the reaction. After the reaction was completed, 140 ml of heptane was added to the reaction mixture. The solution was cooled to 100°C, carefully quenched with 12 ml of water and stir...

Embodiment 1-2

[0101] 11.1 g of cytosine, 63 ml of hexamethyldisilazane and 63 mg of ammonium sulfate were mixed and refluxed for 2 hours. To the resulting mixture was added 60 ml of toluene and heated to remove remaining unreacted hexamethyldisilazane. A mixture of 40 ml of octane and 20 ml of diphenyl ether and 3.5 g of 1-α-bromo-2'-deoxy-2',2'-difluoro-D-ribofuranosyl-5 obtained in Preparation 1 were added to the resulting solution - Benzoyl-3-(4-phenyl)benzoate. The resulting mixture was allowed to react for 10 hours, while diphenyl ether (10 ml) / heptane (1 l) mixture was added dropwise thereto while distillation was performed, and the reaction temperature was maintained at 140-150°C. This step allows the continuous removal of bromotrimethylsilane from the reaction mixture during the course of the reaction. After the reaction was completed, 50 ml of heptane was added to the reaction mixture. The solution was cooled to 80-100°C, 12ml of water was carefully added dropwise, and the mixtu...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to View More

Abstract

This invention relates to an improved method for stereoselectively preparing 2'-deoxy-2',2'-difluorocytidine of formula (I), which comprises the steps of reacting a 1-halo ribofuranose compound of formula (III) with a nucleobase of formula (IV) in a solvent to obtain a nucleoside of formula (II) with removing the silyl halide of formula (V) produced during the reaction; and deprotecting the nucleoside of formula (II) to obtain 2'-deoxy-2',2'-difluorocytidine of formula (I).

Description

field of invention [0001] The present invention relates to a method for the stereoselective preparation of 2'-deoxy-2',2'-difluorocytidine. Background technique [0002] 2'-deoxy-2' of formula (I), 2'-difluorocytidine (gemcitabine) has the cytosine nucleobase (nucleobase) that stereochemistry is directed to β-direction on the 1-position of ribofuranose skeleton, And it is effective in the treatment of various cancers, such as non-small cell lung cancer (NSCLC), pancreatic cancer, bladder cancer, breast cancer or ovarian cancer. [0003] [0004] Gemcitabine can be conventionally prepared as shown in Reaction Scheme 1 from a lactol compound via an active ribofuranose intermediate with a reactive leaving group. [0005] Reaction Scheme 1 [0006] [0007] Among them, P 1 is a hydroxyl protecting group, and L is a leaving group. [0008] Examples of active ribofuranose intermediates for glycosylation are ribofuranose 1-sulfonates such as ribofuranose α-mesylate and 1...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07H19/04
CPCC07H19/04
Inventor 李在宪朴柯胜李文燮方孝正李在哲金哲庆崔敞柱金汉卿李会哲张永佶李宽淳
Owner HANMI SCI CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com