Industrialized gemcitabine hydrochloride synthesis method

A gemcitabine hydrochloride, synthesis technology, applied in the field of gemcitabine hydrochloride synthesis technology, can solve the problem of incomplete reaction, affecting product quality and yield, etc.

Inactive Publication Date: 2013-08-07
湖北一半天制药有限公司
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] But this method is because pass into ammonia gas, and rea...

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
  • Industrialized gemcitabine hydrochloride synthesis method
  • Industrialized gemcitabine hydrochloride synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 2'-deoxy-2', 2'-difluorocytidine-3', 5'-dibenzoate (10g) in methanol (325ml) was cooled to 0°C, 10ml of concentrated ammonia was added, and the reaction was stirred overnight at room temperature , concentrated under reduced pressure, the remaining oil was dissolved in water (100ml), washed with ethyl acetate (100ml×2), the organic layers were combined and extracted with water (100ml), the aqueous layers were combined, decolorized with activated carbon, filtered, and the filtrate was concentrated under reduced pressure to After drying, isopropanol (100ml) and concentrated hydrochloric acid (13ml) were added to the residue, heated to 70°C, kept at room temperature for 0.5h and left to stand overnight. Filtration, the filter cake was washed successively with cold isopropanol (13ml) and n-hexane (6ml), and dried to obtain a white solid, 2'-deoxy-2', 2'-difluorocytidine hydrochloride 4.2g, yield 65%.

[0020] Put 2'-deoxy-2', 2'-difluorocytidine hydrochloride (4.1g) and wat...

Embodiment 2

[0022] 2'-deoxy-2', 2'-difluorocytidine-3', 5'-dibenzoate (20g) in methanol (650ml) was cooled to 0°C, 20ml of concentrated ammonia was added, and the reaction was stirred at room temperature overnight , concentrated under reduced pressure, the remaining oil was dissolved in water (200ml), washed with ethyl acetate (200ml×2), the organic layers were combined and extracted with water (200ml), the aqueous layers were combined, decolorized with activated carbon, filtered, and the filtrate was concentrated under reduced pressure to After drying, isopropanol (200ml) and concentrated hydrochloric acid (26ml) were added to the residue, heated to 70°C, kept at room temperature for 0.5h and left to stand overnight. Filtration, the filter cake was washed successively with cold isopropanol (25ml) and n-hexane (12ml), and dried to obtain a white solid, 2'-deoxy-2', 2'-difluorocytidine hydrochloride 8.1g, yield was 64%.

[0023] Put 2'-deoxy-2', 2'-difluorocytidine hydrochloride (8.1g) an...

Embodiment 3

[0025] 2'-deoxy-2', 2'-difluorocytidine-3', 5'-dibenzoate (40g) in methanol (1300ml) was cooled to 0°C, 40ml of concentrated ammonia was added, and the reaction was stirred overnight at room temperature , concentrated under reduced pressure, the remaining oil was dissolved in water (400ml), washed with ethyl acetate (400ml×2), the organic layers were combined and extracted with water (400ml), the aqueous layers were combined, decolorized with activated carbon, filtered, and the filtrate was concentrated under reduced pressure to After drying, isopropanol (400ml) and concentrated hydrochloric acid (52ml) were added to the residue, heated to 70°C, kept at room temperature for 0.5h and left to stand overnight. Filtration, the filter cake was washed successively with cold isopropanol (50ml) and n-hexane (24ml), and dried to obtain a white solid, 2'-deoxy-2', 2'-difluorocytidine hydrochloride 16g, the yield was 61%.

[0026] Put 2'-deoxy-2', 2'-difluorocytidine hydrochloride (16g)...

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

No PUM Login to view more

Abstract

The invention relates to an industrialized gemcitabine hydrochloride synthesis method, and belongs to the field of chemical product synthesis process. According to the invention, 2'-deoxy-2',2'-difluorocytidine-3',5'-dibenzoate is subjected to benzoyl protecting group removing in a methanol solution comprising ammonia water, and salt-formation is proceeded, such that 2'-deoxy-2',2'-difluorocytidine hydrochloride is formed; and crystallization and separation is carried out in an acetone-water mixed solvent, such that a gemcitabine hydrochloride pure product is obtained. According to the invention, a commonly used method for adding ammonia gas in the step 1 is changed into adding concentrated ammonia water; and a freezing crystallization overnight operation is adopted in subsequent purification process, such that process operability is increased, and reaction yield is improved. The synthesized process product has high refined rate. The purity of the product is maintained above 99.8%.

Description

technical field [0001] The invention relates to a synthesis process of industrially produced gemcitabine hydrochloride. Background technique [0002] Gemcitabine hydrochloride, the chemical name is 2′-deoxy-2′, 2′-difluorocytidine hydrochloride, and the English name is gemcitabine hydrochloride. It is a pyrimidine nucleoside analog developed by Eli Lilly Company in the United States. It was released in Australia and Finland in 1995 Listed in other countries, the trade name is Gemzar. my country has now approved the import, and the Chinese product name is Jianze. The structure of this product is similar to that of cytarabine, which belongs to nucleoside anti-metabolism and anti-tumor drugs. It can penetrate into DNA to break the chain and play a cytotoxic effect. At present, the main synthetic processes are: [0003] [0004] But this method is because feeds ammonia gas, and reaction is incomplete, affects the quality and productive rate of product. Contents of the in...

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): C07H19/073C07H1/00
CPCY02P20/55
Inventor 易镇海李方芝
Owner 湖北一半天制药有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap