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

Preparation method of drug sitagliptin for treating diabetes

A technology of sitagliptin and compounds, applied in the field of western medicine synthesis, can solve the problems of cumbersome reaction routes of sitagliptin, expensive raw materials, harsh reaction conditions, etc., achieve high yield, easy operation of the reaction process, and reduction of by-products Effect

Active Publication Date: 2021-07-23
THE SECOND PEOPLES HOSPITAL OF SHENZHEN
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The technical problem to be solved by the present invention is aimed at the problems in the prior art that the reaction route of sitagliptin is relatively cumbersome, some reaction conditions are relatively harsh, the reaction route is long, the raw material price is relatively expensive, the yield is low, and the product purity is not high.

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 drug sitagliptin for treating diabetes
  • Preparation method of drug sitagliptin for treating diabetes
  • Preparation method of drug sitagliptin for treating diabetes

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0027] The invention discloses a preparation method of sitagliptin, which can be realized by those skilled in the art by referring to the contents of this article and appropriately improving process parameters. It should be pointed out that all similar replacements and modifications will be obvious to those skilled in the art, and they are all considered to be included in the present invention, and relevant persons can obviously make changes without departing from the content, spirit and scope of the present invention. Changes or appropriate changes and combinations are made to the content described herein to realize and apply the technology of the present invention.

[0028] In the present invention, unless otherwise specified, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art.

Embodiment 1

[0030] Embodiment 1: the preparation of formula II compound

[0031]

[0032] In 100mL tetrahydrofuran, under the protection of nitrogen, add compound I 5.92g (24mmol) and 4.44g (36mmol) NH 2 -OBn, stirred at room temperature for 1 hour, then added 0.11g (0.18mmol) [(p-cymene)RuCl 2 ] 2 And 0.049g (0.09mmol) (R,S)-t-Butyl Josiphos, continue to stir for 0.5 hours, finally add 6.81g (50mmol) ZnCl 2 and 5.88g (94mmol) NaBH 3 CN, continue to stir for 20 minutes, heat to reflux, TLC monitors the reaction process, after the reaction is completed, the excess reducing agent is quenched with a saturated ammonium chloride solution, filtered, washed with water, the organic phase is concentrated under reduced pressure, and 6.25g of compound II is obtained by column chromatography (17.7 mmol), yield 74%, e.e. >99.9%.

[0033] 1 H NMR (CHCl 3 -d,400M)δ: 7.32-7.45(m,5H),6.69(s,1H),6.65(s,1H),5.45(s,3H),4.77(s,2H),4.35(d,2H) ,3.44(m,1H),2.69(d,2H); 13 C NMR (CHCl 3-d,400M)δ: 173.1...

Embodiment 2

[0034] Embodiment 2: the preparation of formula III compound

[0035]

[0036] In a high-pressure reactor, 5.31g (15mmol) of compound II in 100mL of chloroform was subjected to hydrogenation reduction reaction on palladium carbon for 6 hours, filtered, washed with an appropriate amount of chloroform, and the filtrate was transferred to a round-bottomed flask, adjusted to pH 4 with hydrochloric acid, and refluxed. After 6 hours, adjust the pH to 6.8 with sodium hydroxide solution, separate layers, add anhydrous magnesium sulfate to the organic phase and dry overnight, and remove the solvent under reduced pressure to obtain 2.71 g (11.6 mmol) of compound III with a yield of 77%.

[0037] 1 H NMR (CHCl 3 -d,400M)δ: 6.81(s,1H),6.65(s,1H),3.34(m,1H),2.92(d,2H),2.34(d,2H); 13 C NMR (CHCl 3 -d,400M)δ:177.1,157.8,147.4,145.2,122.9,118.5, 106.8,48.3,46.6,37.1; MS-ESI(m / z):234.04[M+H] + .

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 present invention provides a method for preparing sitagliptin with a shorter route, through reductive amination with borohydride in the presence of a chiral ligand to obtain a chiral amine compound, and then N-hydroxysuccinimide The activation of the carboxyl group reduces the occurrence of side reactions and obtains a high-yield, high-purity sitagliptin product. The reaction raw materials are cheap and easy to obtain, the reaction process is easy to operate, the yield of each step is high, the product purity is high, and the production cost is reduced. Conducive to industrialized production.

Description

technical field [0001] The application relates to a preparation method of sitagliptin, a drug for treating diabetes, and belongs to the field of western medicine synthesis. Background technique [0002] In recent years, the incidence of diabetes has increased year by year, and diabetes has become another non-communicable disease that seriously threatens human health after cardiovascular diseases and malignant tumors. The type II incidence of diabetes accounts for 90%, and the pathogenesis of type II diabetes is mainly caused by the human body's resistance to insulin and insulin and cell function defects. Clinically used drugs for the treatment of type II diabetes mainly include insulin secretion promoters, sulfonylureas, meglitinides, insulin sensitizers, insulin and insulin receptor agonists and dipeptidyl peptidase-4 inhibitors . [0003] Sitagliptin is the first dipeptidyl peptidase-4 inhibitor developed by Merck Sharp & Dohme Ltd, which was launched in the United State...

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): C07D487/04
Inventor 阎德文谭回左馨
Owner THE SECOND PEOPLES HOSPITAL OF SHENZHEN