Preparation method of tofacitinib citrate

A technology of tofacitinib and citric acid, applied in the field of chemical substances, can solve the problems of many side reactions, low yield, high cost of raw materials, etc., and achieve the effect of easy operation, high yield and low cost

Inactive Publication Date: 2018-08-03
南京法恩化学有限公司
View PDF3 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The literature reports the synthesis methods of tofacitinib citrate and its key intermediates, but these methods have som

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
  • Preparation method of tofacitinib citrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0025] The technical solutions in the present invention are clearly and completely described below in conjunction with the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

[0026] The present embodiment provides a kind of preparation method of tofacitinib citrate, such as figure 1 As shown, it specifically includes the following steps:

[0027] Step 1: Add 100ml of dichloromethane to the reaction flask, then add 10g of 4-chloro-7-pyrrolo[2,3-d]pyrimidine, then add 10g of triethylamine, then dropwise add 15g of (BOC) 2 O, stirred at room temperature, controlled reaction, after the reaction, concentrated the reaction solution, crystallized, filtered, washed with water, dried to obtain 18g of intermediate 1, the yield was 95%;

[0028] Step 2: Add 15g of intermediate 1 to 100ml DMF, add 25g of potassium c...

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 preparation method of tofacitinib citrate, in particular to high-yield synthesis of tofacitinib citrate. The tofacitinib citrate is synthesized from raw materials including4-chloro-7-pyrrolo[2,3-d]pyrimidine, (BOC)2O, (3R,4R)-(1-benzyl-4-methylpiperidine-3-yl)methylamine-L-di-p-toluoyl tartrate, Pd/C, cyanoacetic acid and citric acid through six steps including an aminoprotection reaction, an amination reaction, a debenzylation reaction, a condensation reaction, a deprotection reaction and a salt forming reaction. The synthesis route provides the preparation methodof tofacitinib citrate, and the preparation method is high in yield, low in cost, easy to operate and suitable for industrialization.

Description

technical field [0001] The invention relates to the field of chemical substances, in particular to a preparation method of tofacitinib citrate. Background technique [0002] Tofacitinib citrate, the Chinese chemical name is 3-[(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidine- 4-yl)amino]piperidin-1-yl]-3-oxopropionitrile citrate is a new type of oral Janus kinase (JAK) inhibitor developed by Pfizer, and its inhibitory strength to JAK3 is the same as that of 2 to 5 times that of JAK1 and JAK2. The drug was approved by the U.S. FDA in November 2012 through Risk Evaluation and Mitigation Strategy (REMS). It is used for adults with moderate to severe rheumatoid arthritis (RA) who are active and have poor response to methotrexate. The trade name is For Xeljanz. Tofacitinib is different from other rheumatoid arthritis drugs that act on extracellular targets. It targets intracellular signal transduction pathways and acts on the core part of the cytokine network. In addit...

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): C07D487/04
CPCC07D487/04
Inventor 王坤鹏陈晨张有成
Owner 南京法恩化学有限公司
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