Preparation method of saxagliptin intermediate

A technology of compound and hydroxyl protecting group, which is applied in the field of preparation of saxagliptin intermediates, can solve the problems of harsh conditions, strong corrosion, and low reaction yield, and achieve low price, mild reaction conditions, and high reaction yield Effect

Active Publication Date: 2014-10-15
浙江四维医药科技有限公司
View PDF5 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This route is the method provided in the Chinese patent with the authorized announcement number CN1213028. The SuperHyride reduction used in the synthesis process of this method is extremely harsh. The reaction temperature is -50 ° C. LiEt 3 NBH is flammable, and the elimination reaction uses trifluoroacetic anhydride, which is expensive, highly corrosive, and the reaction yield is low. The Simmons-Smith cyclopropanation reaction used requires the use of reagent diethyl zinc, which requires anhydrous and oxygen-free operation

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 saxagliptin intermediate
  • Preparation method of saxagliptin intermediate
  • Preparation method of saxagliptin intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: S-2-benzylamino-pent-4-en-1-ol

[0043] S-2-amino-pent-4-en-1-ol (5.16g, 51.0mmol), benzaldehyde (6.0g, 56.6mmol) and 30mL methanol were placed in a 100ml two-necked round bottom flask, and the reactant was heated to The reaction was carried out at 40° C. for 12 hours. The reaction mixture was cooled with an ice bath and sodium borohydride (2.65 g, 70.0 mmol) was slowly added, and the reaction was continued for 3 hours after the addition. After the reaction was completed, 10 mL of water was added to quench the reaction, the solvent was removed under reduced pressure, and 30 mL of ethyl acetate was added, washed with water and dried to obtain 9.48 g of S-2-benzylamino-pent-4-en-1-ol with a yield of 97.3%. .

Embodiment 2

[0044] Example 2: S-2-benzylamino-2-formyl-pent-4-en-1-ol

[0045] The substrate S-2-benzylamino-pent-4-en-1-ol (3.0 g, 15.7 mmol) and 30 mL of ethyl formate were placed in a 50 mL single-necked round-bottomed flask, and the reactants were heated to reflux for 24 hours. After the reaction is completed, the solvent is removed to obtain 3.5 g of crude S-2-benzylamino 2-formyl-pent-4-en-1-ol, which can be directly carried out to the next step of the reaction.

Embodiment 3

[0046] Example 3: S-2-benzylamino-2-formyl-1-tert-butyldimethyloxy-pent-4-ene

[0047] The crude product S-2-benzylamino 2-formyl-pent-4-en-1-ol (3.0 g, 13.7 mmol), imidazole (1.87 g, 27.4 mmol) and 20 mL of dichloromethane were placed in 100 mL of two round bottoms In the flask, tert-butyldimethylsilyl chloride (3.1 g, 20.6 mmol) was dissolved in 10 mL of dichloromethane and slowly added dropwise. After the dropwise addition, the reaction was performed for 3 hours, and the reaction end point was determined by thin layer chromatography. After the reaction was completed, 15 mL of water was added to quench and stirred for 0.5 hours. The organic phase was separated, washed with water and dried. After removing the solvent, crude product S-2-benzylamino 2-formyl-1-tert-butyldimethyloxy-pentane was obtained. -4-ene 6g, the crude product was purified by column chromatography to obtain product 4.5g, yield 98.7%.

[0048] 1 HNMR (CDCl 3 ,400MHz)δ(ppm):δ-0.014-0.007(m,6H),2.27-2.38(m...

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 elates to the medicine synthesis field, and concretely relates to a preparation method of a saxagliptin intermediate. A technical scheme adopted in the invention is characterized in that a compound with the structure represented by formula (I) shown in the specification; and in the formula (I), M is hydrogen or various ether hydroxy protection groups, R1 and R2 are H or CH3 respectively independently, and at least one of R1 and R2 is H.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis, in particular to a preparation method of a saxagliptin intermediate. Background technique [0002] Saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a drug developed by Bristol-Myers Squibb for the treatment of adult type II diabetes. Its structural formula is as follows: [0003] [0004] Saxagliptin [0005] Under normal circumstances, saxagliptin is subjected to a condensation reaction by the following formula M and formula N compounds, such as the method disclosed in the US patent document US7223573: the condensation product is dehydrated, and the deprotection group is reacted to obtain saxagliptin, [0006] [0007] Among them, the main synthetic methods of the compound of formula N structure are as follows: [0008] Route one: [0009] [0010] This route is the method provided in the Chinese patent with the authorization announcement number CN1213028. The SuperH...

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): C07C233/18C07C231/02C07C231/12C07D209/52
CPCY02P20/55
Inventor 宗乾收刘新科张斌李原强
Owner 浙江四维医药科技有限公司
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