Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthesis method of antineoplastic drug ribociclib intermediate

A technology of ribociclib and a synthesis method, which is applied in the field of synthesis of antitumor drug intermediates, can solve the problems of long reaction steps and high production costs, and achieve the effects of shortening reaction steps, reducing production costs, facilitating three-waste treatment and industrialized production.

Inactive Publication Date: 2019-10-25
DONGHUA UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] The technical problem to be solved by the present invention is to provide a synthetic method of an antineoplastic drug ribociclib intermediate, to overcome the 2-chloro-7-cyclopentyl-N,N- Defects such as long reaction steps and high production cost of dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

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 method of antineoplastic drug ribociclib intermediate
  • Synthesis method of antineoplastic drug ribociclib intermediate
  • Synthesis method of antineoplastic drug ribociclib intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Synthesis of N,N-Dimethyl-2,3-dibromopropionamide

[0045] Dissolve N,N-dimethylacrylamide (30.0g, 0.30mol) in 200ml of toluene, add bromine (50.4g, 0.30mol) dropwise at room temperature, drop it over in 30 minutes, continue to stir at room temperature for 4h, and the reaction ends The latter toluene layer was washed with water (100 mL×2), dried over anhydrous sodium sulfate, and the toluene was evaporated under reduced pressure to obtain 73.5 g of white solid, yield: 95%.

Embodiment 2

[0047] Synthesis of N,N-Dimethyl-2,3-dibromopropionamide

[0048] Dissolve N,N-dimethylacrylamide (45.0g, 0.45mol) in 250ml of chloroform, add bromine (108.0g, 0.68mol) dropwise at room temperature, drop it over in 30 minutes, continue stirring at room temperature for 2h, and the reaction is complete The latter toluene layer was washed with water (100 mL×2), dried over anhydrous sodium sulfate, and the chloroform was distilled off under reduced pressure to obtain 106.0 g of white solid, yield: 92%.

Embodiment 3

[0050] Synthesis of N,N-Dimethylpropynamide

[0051] Dissolve the N,N-dimethyl-2,3-dibromopropionamide (40.0 g, 0.16 mol) prepared in Example 1 in 200 mL of tetrahydrofuran, cool in an ice bath to 0°C, and add potassium tert-butoxide in batches (18.0g, 0.16mol), add in 30 minutes, rise to room temperature and continue to stir the reaction for 2h, after the reaction is complete, distill off the tetrahydrofuran under reduced pressure, add 100ml of dichloromethane and 100ml of water, stir for 5min, separate the organic layer, Dry over sodium sulfate, evaporate dichloromethane under reduced pressure to obtain 10.6 g of white solid, yield: 68%, mp: 67-70°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 synthesis method of an antineoplastic drug ribociclib intermediate. The synthesis method includes the following steps that the electrophilic addition reaction is conducted on N,N-dimethylacrylamide and bromine to obtain N,N-dimethyl-2,3-dibromopropanamide, then under alkaline conditions, debromination is conducted to prepare N,N-dimethylpropiolamide, and at last the antineoplastic drug ribociclib intermediate is prepared by the reaction with N-cyclopentadienyl-2-chlorine-5-bromine-4-amidepyrimidinyl under the action of a catalyst. According to the synthesis method ofthe antineoplastic drug ribociclib intermediate, the preparation process is easy to operate, yield is high, the reaction route is short, three wastes are less, and industrial production is facilitated.

Description

technical field [0001] The invention belongs to the field of synthesis of antineoplastic drug intermediates, in particular to a method for synthesizing an antineoplastic drug ribociclib intermediate. Background technique [0002] Ribociclib (Ribociclib, I, with the following structure), developed by Novartis Pharmaceuticals, is a selective cyclin-dependent kinase 4 / 6 inhibitor, which can significantly prolong the estrogen receptor-positive, human epidermis in postmenopausal women. Progression-free survival in patients with growth factor receptor-2 negative advanced or metastatic breast cancer. In March 2017, it was approved for marketing by the US Food and Drug Administration (FDA). The product name is Kisqali. The oral dose is 600mg (3 tablets, 200mg per tablet) once a day. After 3 weeks of treatment, the drug is stopped for 1 week. Aromatase inhibitor letrozole and others are used in combination as an initial regimen based on endocrine therapy for the treatment of postmen...

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 Applications(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 赵圣印王文康祝家楠陈樱
Owner DONGHUA UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com