Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tolvaptan intermediate and preparation method thereof

A technology for tolvaptan and an intermediate, which is applied in the field of medicinal chemistry, can solve environmental problems, expensive metal salt by-products and other problems, and achieves the effects of cheap reagents, easy operation and environmental friendliness

Active Publication Date: 2013-10-30
JIANGSU KANION PHARMA CO LTD +1
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Disposal of metal salt by-products can be expensive and cause serious environmental concerns

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
  • Tolvaptan intermediate and preparation method thereof
  • Tolvaptan intermediate and preparation method thereof
  • Tolvaptan intermediate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine ( Preparation of formula (I) compound)

[0034] In a 100mL four-neck round bottom flask equipped with a magnetic stirrer and a thermometer, add 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4, 5-tetrahydro-1H-1-benzazepine (compound of formula (II)) 4.70g, iron powder 1.60g, 98% concentrated sulfuric acid 4.20g, ammonium sulfate 20.0g, ethanol 50mL. React at 60°C for 5 hours, TLC shows that the reaction is complete, then filter, wash the filter cake with ethanol, combine the filtrates and then rotary evaporate under reduced pressure, add 50 mL of dichloromethane to the obtained product, slowly add saturated sodium bicarbonate solution dropwise, adjust the pH to 7-8, and divide After the liquid, the organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to remove the solvent to obtain 4.10 g of the compound of formula (II) as a pale...

Embodiment 2

[0037] Embodiment 2: 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine ( Preparation of formula (I) compound)

[0038] In a 100mL four-neck round bottom flask equipped with a magnetic stirrer and a thermometer, add 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4, 4.70 g of 5-tetrahydro-1H-1-benzazepine (compound of formula (II)), 1.90 g of zinc powder, 4.50 g of 98% concentrated sulfuric acid, 20.0 g of ammonium sulfate, and 50 mL of ethanol. React at 60°C for 4 hours, filter after TLC shows that the reaction is complete, wash the filter cake with ethanol, combine the filtrates, and then rotary evaporate under reduced pressure. After the liquid, the organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to remove the solvent to obtain 4.00 g of the compound of formula (II) as a pale yellow foamy solid, mp 190-191°C, yield 93.8%.

Embodiment 3

[0039] Embodiment 3: 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine ( Preparation of formula (I) compound)

[0040] In a 100mL four-neck round bottom flask equipped with a magnetic stirrer and a thermometer, add 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4, 2.0 g of 5-tetrahydro-1H-1-benzazepine (compound of formula (II)), 0.7 g of iron powder, 2.5 g of 70% concentrated sulfuric acid, 8.5 g of ammonium sulfate, and 25 mL of ethanol. React at 60°C for 4 hours, filter after TLC shows that the reaction is complete, wash the filter cake with ethanol, combine the filtrates, and then rotary evaporate under reduced pressure. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to remove the solvent to obtain 1.44 g of the compound of formula (II) as a light yellow foamy solid, mp 190-191°C, yield 79.5%.

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 relates to the field of pharmaceutical chemistry and particularly discloses preparation methods for a tolvaptan intermediate 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine (I) (shown in the description) and salts thereof. The tolvaptan intermediate prepared by utilizing the method disclosed by the invention has the characteristics of low cost, high yield, environmental friendliness, strong operability and suitability for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to an intermediate 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4, which is used for the synthesis of tolvaptan. The preparation method of 5-tetrahydro-1H-1-benzazepine (I) and its salt. Background technique [0002] Tolvaptan (Tolvaptan), the chemical name is 7-chloro-5-hydroxy-1-[2-methyl-4-[(2-methylbenzoyl)-amino]benzoyl] 2,3, 4,5-tetrahydro-1H-1-benzazepine, its structural formula is as shown in formula (IV): [0003] [0004] Tolvaptan is a novel oral non-peptide arginine vasopressin (AVP) V2 receptor antagonist developed by Otsuka Pharm. AVP V2 receptor antagonists can promote the excretion of water in the patient's body without affecting the electrolyte balance in the patient's body. of hyponatremia. The drug was approved by the FDA on May 19, 2009. [0005] The preparation method of the original research company Japan Otsuka Pharmaceutical Co., Ltd. (Bioorg.Med....

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
IPC IPC(8): C07D223/16
Inventor 张福利梁小敏萧伟吴泰志郭庆明姜学书陈昊张伟
Owner JIANGSU KANION PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com