Preparation method of ramelteon

A technology of ethylamine and compounds, applied in the field of medicinal chemistry, can solve the problems of low total reaction yield and many reaction steps, and achieve the effect of simple operation, single type and high yield

Inactive Publication Date: 2020-05-19
BEIJING VENTUREPHARM BIOTECH
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the traditional preparation process of ramelteon, the existence of chiral resolution steps leads to low overall yield of reaction and more reaction steps

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 ramelteon
  • Preparation method of ramelteon
  • Preparation method of ramelteon

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Weigh 100.00 g of 1,6,7,8-tetrahydro-8H-indeno[5,4-b]furan-8-one, 122.03 g of diethyl cyanomethylphosphonate, and 130.27 g of sodium methoxide. Keep the temperature at 35 °C, stir for 12 h, then add 2 L of water, stir for 4 h, then filter, wash the filter cake with 200 ml of water, and dry at 50 °C for 24 h. 98 g of white solid was obtained.

[0036] 90.00 g of the white solid obtained above was dispersed by adding 540 ml of methanol, and [Et 2 NH 2 ] + [Ru 2 Cl 5 (BINAP) 2 ] - 1.66 g. After the addition, pass hydrogen to 5 MPa and stir at 50 °C for 20 h. TLC detects that the reaction is complete. After the reaction is complete, the solvent is spin-dried, and then 450 ml of n-heptane is used for slurry, and then filtered. The solid cake is collected and dried at 50 °C for 1 h. In 270 ml of ethyl acetate and 270 ml of n-heptane, dissolved at 50 °C and then crystallized at 0 °C to obtain 90.15 g of yellow oil. The purity of the final product by HPLC was 98.5%.

Embodiment 2

[0038] Weigh 100.00 g of 1,6,7,8-tetrahydro-8H-indeno[5,4-b]furan-8-one, 122.03 g of diethyl cyanomethylphosphonate, and 130.27 g of sodium methoxide. Keep the temperature at 35 °C, stir for 12 h, then add 2 L of water, stir for 4 h, then filter, wash the filter cake with 200 ml of water, and dry at 50 °C for 24 h. 98 g of white solid was obtained.

[0039] 90.00 g of the white solid obtained above was dispersed by adding 540 ml of methanol, and [Ru (BINAP) (OCOCH 3 ) 2 ] 0.86 g, after the addition, pass hydrogen to 5 MPa and stir at 50 °C for 20 h, and the reaction is complete as detected by TLC. Spin to dry the solvent, then beat with 450 ml of n-heptane, then filter, collect the filter cake solids and dry at 50 °C for 1 h, then place in 270 ml of ethyl acetate and 270 ml of n-heptane, dissolve at 50 °C and crystallize at 0 °C 90.15 g of yellow oil were obtained. The purity of the final product by HPLC was 95.3%.

Embodiment 3

[0041] Weigh 100.00 g of 1,6,7,8-tetrahydro-8H-indeno[5,4-b]furan-8-one, 122.03 g of diethyl cyanomethylphosphonate, and 130.27 g of sodium methoxide. Keep the temperature at 35 °C, stir for 12 h, then add 2 L of water, stir for 4 h, then filter, wash the filter cake with 200 ml of water, and dry at 50 °C for 24 h. 98 g of white solid was obtained.

[0042] 90.00 g of the white solid obtained above was dispersed by adding 540 ml of methanol, and [RuCl(BINAP)( p -cymene)]Cl 1.26 g, after the addition was completed, pass hydrogen to 5 MPa and stir at 50 °C for 20 h, and TLC detected that the reaction was complete. Spin to dry the solvent, then beat with 450 ml of n-heptane, then filter, collect the filter cake solids and dry at 50 °C for 1 h, then place in 270 ml of ethyl acetate and 270 ml of n-heptane, dissolve at 50 °C and crystallize at 0 °C 90.15 g of yellow oil were obtained. The purity of the final product by HPLC was 96.2%.

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 belongs to the field of medicinal chemistry, and mainly relates to a (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)-1-ethylamine compound represented by a formula I. The method has the advantages that the operation is simple, the steps are reduced compared with the previous method, the route is shortened, and the used solvent is single in variety, convenient to recycle and high in yield, wherein the formula I is defined in the specification.

Description

technical field [0001] The present invention belongs to the field of medicinal chemistry and mainly relates to (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)- Process for the preparation of 1-ethylamine. Background technique [0002] Ramelteon (Ⅱ) (ramelteon,2), the chemical name is (S)-N-[2-(1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan- 8-yl)] propionamide, developed by Japan's Takeda Company, was approved by the US FDA in September 2005. This product is a melatonin receptor agonist, which can simulate the physiological effects of melatonin secreted by the pineal gland, which helps to regulate the sleep cycle and improve sleep quality. Drugs for the treatment of insomnia. [0003] [0004] II [0005] Currently in the process of preparing ramelteon, often ( E )-2-(1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)acetonitrile was first prepared by catalytic hydrogenation into a racemate, and then manually (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)-1-...

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): C07D307/77
CPCC07D307/77
Inventor 海楠李恩民赵国磊
Owner BEIJING VENTUREPHARM BIOTECH
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