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

A kind of synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile

A synthetic method, 2-b technology, applied in the direction of organic chemistry, etc., can solve the problems of 6-chloroimidazole that has not been disclosed, complex steps of the preparation method, and difficult synthesis, and achieve the effects of easy acquisition, stable product quality, and convenient operation

Active Publication Date: 2022-03-04
HEZE BRANCH QILU UNIV OF TECH(SHANDONG ACAD OF SCI
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] 6-Chlorimidazo[1,2-b]pyridazine-3-carbonitrile is an important intermediate in organic synthesis, mainly used in pharmaceutical intermediates, and in organic synthesis, it is the key intermediate of the new anticancer drug BMS-986260. Due to 6-Chlorimidazo[1,2-b]pyridazine-3-carbonitrile is a novel pharmaceutical intermediate. Although it has great medical value, it is difficult to synthesize. The current preparation method has complicated steps and high cost. And the synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile is not disclosed in the literature published at present, lacks a kind of efficient, high-yield 6-chloroimidazo[1,2-b] now. 2-b] Pyridazine-3-carbonitrile preparation 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 synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile
  • A kind of synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile
  • A kind of synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 50g (390mmol) of 3-amino-6-chloropyridazine is the reaction raw material, react with 400g N-dimethylformamide dimethyl acetal at 60°C for 4 hours, and the reaction is completed to obtain N,N-dimethyl -N'-3-(6-chloro-pyridazinyl)-formamidine intermediate, remove excess N,N-dimethylformamide dimethyl acetal by rotary evaporation, add DMF400ml and drop bromoacetonitrile (60.8g , 507mmol), reacted at 60°C for 10 hours, after the reaction was completed, cooled to room temperature, added an appropriate amount of saturated sodium bicarbonate solution, adjusted the pH to 7.9, stood for three hours, and precipitated solids, dissolved all the solids in 300ml of ethyl acetate , washed three times with water, 100ml each time, then washed twice with saturated brine, 100ml each time, then dried with anhydrous sodium sulfate, concentrated by rotary evaporation, mixed with n-hexane:ethyl acetate volume ratio of 1:2 The solution was recrystallized to obtain 58.1 g of pure product. The ...

Embodiment 2

[0024] 50g (390mmol) of 3-amino-6-chloropyridazine is the reaction raw material, react with 400g N-dimethylformamide dimethyl acetal at 110°C for 3 hours, and N,N-dimethyl -N'-3-(6-chloro-pyridazinyl)-formamidine intermediate, remove excess N,N-dimethylformamide dimethyl acetal by rotary evaporation, add DMF400ml and drop bromoacetonitrile (60.8g , 507mmol), reacted at 80°C for 8 hours, after the reaction was completed, cooled to room temperature, added an appropriate amount of saturated sodium bicarbonate solution, adjusted the pH to 8.3, stood for three hours, and precipitated solids, dissolved all the solids in 300ml of ethyl acetate , washed three times with water, 100ml each time, then washed twice with saturated brine, 100ml each time, then dried with anhydrous sodium sulfate, concentrated by rotary evaporation, mixed with n-hexane:ethyl acetate volume ratio of 1:2 The solution was recrystallized to obtain 55.5 g of pure product. The purity is 99.1%, and the yield is 79...

Embodiment 3

[0026] 50g (390mmol) of 3-amino-6-chloropyridazine is the reaction raw material, react with 400g N-dimethylformamide dimethyl acetal at 50°C for 8 hours, and N,N-dimethyl -N'-3-(6-chloro-pyridazinyl)-formamidine intermediate, remove excess N,N-dimethylformamide dimethyl acetal by rotary evaporation, add 400ml of acetonitrile and drop bromoacetonitrile (60.8 g, 507mmol), reacted at 100°C for 10 hours, after the reaction was completed, cooled to room temperature, added an appropriate amount of saturated sodium bicarbonate solution, adjusted the pH to 7.4, stood for three hours, and precipitated solids, dissolved all solids in 300ml ethyl acetate in water, washed three times with 100ml each time, then washed twice with saturated brine, 100ml each time, then dried with anhydrous sodium sulfate, concentrated by rotary evaporation, and the volume ratio of n-hexane:ethyl acetate was 1:2 The mixed solution was recrystallized to obtain 54.2 g of pure product. The purity is 98.5%, and ...

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

A synthetic method for 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile, comprising the steps of: Step 1: adding N,N-dimethylformamide dimethyl acetonitrile to the reactor Aldehyde reacts with 3-amino-6-chloropyridazine to obtain N,N-dimethyl-N'-3-(6-chloro-pyridazin) base-formamidine intermediate; step 2: the resulting N,N-dimethyl-N'-3-(6-chloro-pyridazine) base-formamidine intermediate is mixed with solvent, added bromoacetonitrile, reacted, added lye, left standing, precipitated solid, filtered, and obtained Solid mixture; Step 3: The solid mixture obtained in Step 4 is completely dissolved in ethyl acetate, washed with water and saturated brine, dried, filtered, and ethyl acetate is removed to obtain 6-chloroimidazo[1,2-b] Pyridazine‑3‑carbonitrile crude product; step 4: recrystallize 6‑chloroimidazo[1,2‑b]pyridazine‑3‑carbonitrile crude product, filter to obtain 6‑chloroimidazo[1,2‑b ] Pyridazine‑3‑carbonitrile pure product. The whole process of the invention is short in time, and the obtained product has stable quality and high purity.

Description

technical field [0001] The invention belongs to the field of synthesis of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile, specifically a kind of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile synthetic method. Background technique [0002] 6-Chlorimidazo[1,2-b]pyridazine-3-carbonitrile is an important intermediate in organic synthesis, mainly used in pharmaceutical intermediates, and in organic synthesis, it is the key intermediate of the new anticancer drug BMS-986260. Due to 6-Chlorimidazo[1,2-b]pyridazine-3-carbonitrile is a novel pharmaceutical intermediate. Although it has great medical value, it is difficult to synthesize. The current preparation method has complicated steps and high cost. And the synthetic method of 6-chloroimidazo[1,2-b]pyridazine-3-carbonitrile is not disclosed in the literature published at present, lacks a kind of efficient, high-yield 6-chloroimidazo[1,2-b] now. 2-b] Pyridazine-3-carbonitrile preparation method. Contents of the invention ...

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
CPCC07D487/04
Inventor 程伟杨德亮祁祺王明君王俊方魏国富赵浩郑爽
Owner HEZE BRANCH QILU UNIV OF TECH(SHANDONG ACAD OF SCI
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