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

A kind of high-efficiency preparation method of mixed lacosamide

A lacosamide, high-efficiency technology, applied in the field of lacosamide preparation, can solve the problems of complex steps, long route, easy allergies, etc., and achieve the effect of high atom utilization rate, good economic benefit and simple post-treatment

Active Publication Date: 2021-04-06
天台宜生生化科技有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the classification of starting materials, there are mainly the following routes: (1) Use Boc-protected D-serine as raw material to synthesize lacosamide (EP1642889A1) through methyl etherification, amidation, deprotection and amidation. The classic synthetic route is also the commonly used industrialized process route at present; (2) Starting from benzyloxymethyl oxirane, it undergoes ring-opening etherification, azidation, hydrogenation, Boc protection, hydroxyl oxidation, Amidation, and finally deprotection, acetylation to synthesize lacosamide (US20140012044A1), the route is long and complicated, the yield is low, and it is not suitable for industrial production; One-step reaction (WO2016125178A1), or using halomethyl propylene oxide as raw material to synthesize lacosamide through 7-step reaction (WO2016030911A2), both of which have the problem that the route is too long and the steps are complicated; (3) N-benzyl acrylamide Lacosamide (WO2012069855A1) is synthesized from alkenes as raw materials through halogenation, methoxylation, ammoniation, and finally acetylation (WO2012069855A1), which is also a commonly used industrialization method, but liquid bromine is used in this method.

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
  • A kind of high-efficiency preparation method of mixed lacosamide
  • A kind of high-efficiency preparation method of mixed lacosamide
  • A kind of high-efficiency preparation method of mixed lacosamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]Example 1: Synthesis of 2-acetylamino-3-methoxypropionate

[0029]According to the amount of substance than N-acetyl varinethine: bromine: sodium hydride is 1.0: 2.0: 3.0.0: N-acetyl varinethrine 44.1 g, bromine 57.0 g, sodium hydride 36.0 g; anhydrous organic solvent A is DMF 660ml, The volume of volume is 15 times (ml / g) of N-acetyl.

[0030]In a dry clean reaction bottle, nitrogen gas protection, slowly add DMF, sodium hydride and N-acetyl hydrogen, stir, and ice salt bath to -10 ~ -5 ° C, slowly introduced into bromomethane, control the reaction temperature at 0 ° C the following. After the dropwise addition, the reaction was at 80 ° C for 3 hours. The reaction liquid was quenched, and then methyl tert-butyl ether extraction was added, and the organic phase was concentrated to concentrate 2-acetamin-3-methoxypropathic acid methyl ester intermediate 36.8 g, yield of 70.0%.

Embodiment 2

[0032]According to the amount of substance than N-acetylsenine: sodium bromine: sodium hydride is 1.0: 2.0: 2.1, N-acetyl variarine 44.1 g, bromine 57.0 g, sodium hydride 25.2 g; anhydrous organic solvent A is DMSO 880ml, The volume of volume is 20 times (mL / g) of N-acetylithine mass.

[0033]The reaction temperature was 20 ° C, and the reaction was 10 hours, and other operations were operated in Example 1, 2-acetamin-3-methoxypropionate 42.5 g, yield 80.9%.

Embodiment 3

[0035]According to the amount of substance than N-acetylacetine: bromine: sodium hydride is 1.0: 2.5: 3.5, N-acetylacetine 44.1 g, bromine 71.2 g, sodium hydride 42.0 g; anhydrous organic solvent A is N, N- Dimethyl acetamide 660 ml of its volume of 15 times (ml / g) of N-acetyl raw serine mass.

[0036]The reaction temperature was 40 ° C, and the reaction was 8 hours, and other operations were operated in Example 1, 2-acetamin-3-methoxypropionate 42.0 g, yield of 79.9%.

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 discloses a high-efficiency preparation method of mixed-rotating lacosamide, which is characterized in that the preparation method is as follows: using N-acetylserine represented by formula (II) as a raw material, first under the action of sodium hydride Complete reaction with methyl bromide to obtain methyl 2-acetamido-3-methoxypropionate represented by formula (III), and then transesterify with benzylamine under the catalysis of trifluoromethanesulfonate to obtain the product Mixed lacosamide. The preparation method of the mixed-rotating lacosamide of the present invention has an industrialized process route with short reaction route, high yield, high atom utilization rate, simple post-treatment and low cost.

Description

Technical field[0001]The present invention discloses a method of preparing a mixed puller amide.Background technique[0002]Lacosamide, chemical nameR- (-) - 2-acetyl amino-3-methoxy-N-benzyl amide is the third-generation drug developed by Belgium UCB Pharmaceutical Co., Ltd., which is a drug that treats epilepsy and neurosal pain. The medicine was in September 2008. And October 2008, the European Commission and the US Food and Drug Administration (FDA) were obtained respectively. The drug has a unique dual role mode to stabilize the super excitatory nerve cell membrane and inhibit the neuronal repeated discharge, different from other antiepileptic drugs used in clinical practice, which can be used for an auxiliary treatment of partial seizures of epilepsy in 16 years old It is widely concerned.[0003][0004]At present, there are many ways to synthesize laculatamides at home and abroad. Classification according to the starting materials, mainly include the following routes: (1) is a raw...

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): C07C231/02C07C237/22C07C231/12C07C233/47
CPCC07C231/02C07C231/12C07C237/22C07C233/47
Inventor 夏建胜孙坚方元文陈斌陈德响何亚文
Owner 天台宜生生化科技有限公司