Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of fused pyrazole compound

A technology for compounds and derivatives, applied in the field of organic synthesis, can solve the problems of difficult process production, poor selectivity, cumbersome operation, etc., and achieve the effects of improving yield and economy, avoiding safety risks, and having strong practicability.

Pending Publication Date: 2021-12-24
SHANGHAI MEIYUE BIOTECH DEV
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of preparation method has been proved to have significant defects: 1) This type of method has poor selectivity, and will produce a mixed product of positional isomers in which the 1-position and 2-position N of the pyrazole ring are respectively substituted, and the yield is low; 2) Since the polarity and other characteristics of the above-mentioned positional isomers are relatively close, post-processing and separation are relatively difficult, and column chromatography purification and separation are often required, which is difficult to achieve technological production; 3) This type of reaction is SN 2 Reaction mechanism, if the structure of the alkyl group is relatively large, the reaction may be more difficult
However, the above-mentioned method uses a dimethyl sulfoxide solution with a higher boiling point, and water and a low-boiling organic solvent need to be added in the post-reaction treatment for extraction, and the operation is relatively cumbersome.
Moreover, this method needs to concentrate the intermediate product of azide, and there are safety risks such as explosion
Further, because the above method needs to remove molecular sieves and dichloromethane, and then heat in toluene to produce intermediate 3, the process is relatively complicated, and the post-treatment still needs to be purified by column chromatography, the efficiency is low, and it is not suitable for large-scale production

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 fused pyrazole compound
  • Preparation method of fused pyrazole compound
  • Preparation method of fused pyrazole compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Example 1: Preparation of 2-[3-(6-methoxy-5-nitro-indazol-2-yl)-cyclobutyl]-trans-propyl-2-alcohol

[0101]

[0102] 2-Fluoro-4-methoxy-5-nitrobenzaldehyde (10.00g) and sodium azide (3.60g) were sequentially added to methanol (100mL) solution, and the reaction mixture was stirred at 20-30°C for 16 hours. Without further treatment, the reaction mixture was a methanol solution of 2-azido-4-methoxy-5-nitrobenzaldehyde (50.00 mmol, based on a yield of 100%). To the above methanol solution of 2-azido-4-methoxy-5-nitrobenzaldehyde was added 2-(3-amino-cyclobutyl)-trans-propyl-2-ol (4.66 g) and concentrated Sulfuric acid (5.00g, 98%), keep the system reflux for 3 hours, the reaction temperature is 72-77 ° C, add water (40mL) to the reaction system, concentrate the mixed solution to a certain volume (40mL) under vacuum, after cooling, filter, The filter cake was dried to obtain 2-[3-(6-methoxy-5-nitro-indazol-2-yl)-cyclobutyl]-trans-propyl-2-alcohol (10.80g, two steps Yiel...

Embodiment 2

[0103] Example 2: Preparation of 2-[3-(6-methoxy-5-amino-indazol-2-yl)-cyclobutyl]-trans-propyl-2-alcohol

[0104]

[0105] Add 2-[3-(6-methoxy-5-nitro-indazol-2-yl)-cyclobutyl]-trans-propyl-2-ol (10.00g) to absolute ethanol (100mL) , under the protection of nitrogen, add palladium carbon (0.50g, anhydrous, 10% load rate), then replace with hydrogen, stir at 25-30°C for 3 hours under the pressure of a hydrogen balloon (1 atmosphere), add diatomaceous earth and filter, The filtrate was concentrated to give 2-[3-(6-methoxy-5-amino-indazol-2-yl)-cyclobutyl]-trans-propyl-2-ol (8.73g, yield: 96.1%) . 1 H NMR (400MHz, DMSO): δ7.90(s,1H),6.87(s,1H),6.62(s,1H),4.87(p,J=7.31Hz,1H),4.58(s,2H), 4.37(s,1H),3.82(s,3H),2.48(dd,J=16.43,8.83Hz,4H),2.44-2.32(m,1H),1.18-1.02(m,6H); LCMS m / z =276[M+H] + .

Embodiment 3

[0106] Example 3: 6-Trifluoromethyl-pyridine-2-carboxylic acid {2-[3'-(1-hydroxy-1-methyl-ethyl)-cyclobutyl]-6-methoxy-2 Preparation of Hydrogen-Indazol-5-yl}-amides

[0107]

[0108] 2-[3-(6-Methoxy-5-amino-indazol-2-yl)-cyclobutyl]-trans-propyl-2-ol (8.25 g) was added to tetrahydrofuran (60 mL), then Add 5-trifluoromethyl-2-pyridinecarboxylic acid (5.73g), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate in sequence (12.55g) and N,N-diisopropylethylamine (4.27g), the reaction mixture was stirred at room temperature for 4 hours, water (120mL) was added, filtered, and the filter cake was dried to obtain compound 1 (11.49g, Yield: 85.4%). 1 HNMR (400MHz, CDCl 3 ): δ10.71(s,1H),8.81(s,1H),8.50(d,J=8.0Hz,1H),8.11(t,J=8.0Hz,1H),7.89(s,1H),7.86 (d,J=6.8Hz,1H),7.11(s,1H),5.05-4.99(m,1H),4.03(s,3H),2.79-2.72(m,2H),2.67-2.60(m,3H ), 1.34(s,1H), 1.25(s,6H); LCMS m / z=449.2[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 invention provides a 2-nitrogen-substituted fused pyrazole compound, and particularly relates to a one-pot preparation method of a 2-nitrogen-substituted indazole compound. According to the process, after halogen in a substrate is subjected to azidation, R-NH2 is directly added and subjected to ring closing with an aldehyde group without after-treatment. For example, with 2-fluoro-4-methoxy-5-nitrobenzaldehyde as a raw material, a 2-nitrogen-substituted indazole compound can be obtained through azidation and ring closing, and then a series of indazole derivatives are obtained through hydrogenation and condensation reactions. The process method is simple in steps and simple to operate, has certain universality to different substrate structures, and is suitable for technologized large-scale production.

Description

[0001] This application claims to enjoy the patent of the previous application submitted by the applicant to the State Intellectual Property Office of China on June 23, 2020, the patent application number is 202010581690. priority. The entirety of this application is incorporated by reference into this application. technical field [0002] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of condensed pyrazole compounds. Background technique [0003] In the existing preparation method of the condensed pyrazole compound substituted by the 2-position nitrogen, especially the indazole compound substituted by the 2-position nitrogen, it is relatively common at present to carry out the substitution reaction of the indazole substrate by an alkyl halide. preparation. However, this type of preparation method has been proved to have significant defects: 1) This type of method has poor selectivity, and will produce a mixed pro...

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): C07D401/12A61K31/4439A61K31/4709A61P29/00A61P37/00A61P35/00
CPCC07D401/12A61P29/00A61P37/00A61P35/00C07D231/56
Inventor 野国中田勇傅仕康孙宗国陈永凯王朝东
Owner SHANGHAI MEIYUE BIOTECH DEV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com