Unlock instant, AI-driven research and patent intelligence for your innovation.

Synthesis process for industrial production of capecitabine intermediate

A synthesis process and capecitabine technology are applied in the field of synthetic processes for industrialized production of capecitabine intermediates, and can solve problems such as affecting product quality and yield, unfavorable product separation and purification, poor stability of tribenzoyl chloride hydroxyl groups, and the like , to increase the stability

Active Publication Date: 2015-04-22
南京亚东启天药业有限公司
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] It is a new process, although the raw materials are cheap, but the stability of tribenzoyl chloride (BzCl) to protect the hydroxyl group is relatively poor, which is not conducive to the separation and purification of products, and then affects product quality and yield

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
  • Synthesis process for industrial production of capecitabine intermediate
  • Synthesis process for industrial production of capecitabine intermediate
  • Synthesis process for industrial production of capecitabine intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] (1) Preparation of 5-tert-butyldiphenylsilane-D-ribose 2:

[0045] Under nitrogen protection and stirring, D-ribose (24g, 160mmol), tert-butyldiphenylchlorosilane (49.2g, 179.2mmol), 4-dimethylaminopyridine (0.58g, 4.8mmol), pyridine (150mL ) into a (250mL) flask, reacted at 50~55°C for 6h, then added petroleum ether (150mL), cooled to 0°C, filtered, and the filtrate was concentrated under reduced pressure to obtain yellow oil 2. The yield is 70%. 1 H NMR(DMSO-d6,500MHz)δ:7.66~7.63(m,4H),7.47~7.39(m,6H),5.79~5.78,5.81~5.80(dd,1H,J=1.6Hz and 7.2Hz), 5.27~5.25(d,1H,J=6.4Hz),5.00~4.99(d,1H,J=4.0Hz),4.56~4.52(m,1H),4.35~4.32(m,1H),4.03~4.06( m,1H), 3.90~3.86(m,1H), 3.73~3.69(m,1H), 3.65~3.59(m,1H), 0.98(s,9H).

[0046] (2) Preparation of 2,3-dibenzoyl-5-tert-butyldiphenylsilane-D-ribose 3:

[0047] Under nitrogen protection and stirring, 5-tert-butyldiphenylsilane-D-ribose (38.9g, 100mmol), ethyl acetate (150mL), chloroacetyl chloride (24.8g, 220mmol), 4-dimethyl Add a...

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 a synthesis method of capecitabine, and particularly provides a synthesis process for the industrial production of a capecitabine intermediate. According to the synthesis process for the industrial production of an important capecitabine intermediate, namely, 2', 3', 5'-trihydroxy-5-gemcitabine, D-ribose with low cost is adopted as a raw material, and the intermediate is prepared by hydroxyl groups under the protection of halogenosilane, acyl chloride and sulfonyl chloride, so that the stability of the intermediate is improved, the selectivity is also provided for improving the hydroxyl groups in future, and further, the capecitabine intermediate is applicable to large-scale industrial production.

Description

technical field [0001] The invention relates to a capecitabine synthesis method, and specifically provides a synthesis process for industrial production of capecitabine intermediates. Background technique [0002] Capecitabine (English name: capecitabine), the chemical name is 5'-deoxy-5-fluoro-N-[(pentyloxy)carbonyl] cytidine, a new type of 5-fluorouracil developed by Swiss Hoffmann-LaRoche company The premise drug, which was first launched on the Swiss market in 1998. This product is a new type of oral flucytosine nucleoside analogue, which has no cytotoxicity itself, and is metabolized into 5-fluorouracil (5-FU) under the action of enzymes in the body, and then exerts anti-tumor effect. It is mainly used clinically for the treatment of advanced breast cancer Carcinoma, colon / rectal cancer and other solid tumors, it has good curative effect and strong safety for adjuvant therapy and metastatic tumor treatment. It has been approved by the US Food and Drug Administration (...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/067C07H1/00
Inventor 蔡惠明
Owner 南京亚东启天药业有限公司