Low cost method for preparing sitagliptin phosphate salt key intermediate

A technology of sitagliptin and phosphate, applied in the direction of organic chemistry, etc., to achieve the effect of reducing the amount of waste water, low production cost and less impurities
CN104987338AActive Publication Date: 2015-10-21XINFA PHARMA
6 Cites 6 Cited by

Patent Information

Authority / Receiving Office
CN Β· China
Current Assignee / Owner
XINFA PHARMA
Publication Date
2015-10-21

Smart Images

  • Figure 1
    Figure 1
  • Figure 2
    Figure 2
  • Figure 3
    Figure 3
Patent Text Reader

Abstract

The invention relates to a low cost method for preparing a sitagliptin phosphate salt key intermediate. The method comprises the steps of: with existence of suitable solvents and inorganic bases, preparing 3-oxalysine-[3-(trifluoromethyl)-5,6-dihydrogen[1,2,4]triazolo[4,3-a]pyrazinyl-7(8H)]propionitrile(IV) by reacting cyanoethanoate ester with 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine hydrochloride(III)amidation and removing alcohol; and compound IV then reacting with a Grignard reagent that is prepared by 2,4,5-trifluoro-1-halogenated methyl benzene and magnesium, so as to obtain 4-oxalysine-4-[3-(trifluoromethyl)-5,6-dihydrogen[1,2,4]triazolo[4,3-a]pyrazinyl-7(8H)]-1-(2,4,5-trifluorophenyl)-2-butanone(II). According to the method provided by the invention, the expensive Michaelis acid, trimethylacetyl chloride and diisopropylethylamine are not used; the raw material used is cheap and easy to obtain and has less waste water in the production process; the product is high in yield, has few impurities, and is low in cost.
Need to check novelty before this filing date? Find Prior Art

Description

technical field

[0001] The present invention relates to a low-cost method for preparing sitagliptin phosphate key intermediate 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazinamide derivatives The method belongs to the field of medicine and chemical industry. Background technique

[0002] Since the US FDA approved sitagliptin phosphate for marketing in October 2006, sitagliptin phosphate has been approved for the treatment of type 2 diabetes in 95 countries including China. Sitagliptin phosphate, the chemical name is (3R)-3-amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo [4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one phosphate, CAS number is 654671-78-0, English name is Sitagliptin Phosphate is a dipeptidyl peptidase-1V (DPP-1V) inhibitor developed by Merck & Co. of the United States. The structural formula of sitagliptin phosphate is shown in Formula I.

[0003] Sitagliptin phosphate is the first dipeptidyl enzyme-4 (DPP-4) inhibitor type 2 diabe...

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