Process for preparing substituted imidazo[4,5-c]pyrazoles

Patent metadata

Field	Value
Publication number	US-11987585-B2
Application number	US-202318166898-A
Country	US
Kind code	B2
Filing date	Feb 9, 2023
Priority date	Aug 31, 2021
Publication date	May 21, 2024
Grant date	May 21, 2024

Abstract

The present invention relates to novel fused imidazo pyrazole derivatives of formula (I), and formula (II), and methods for preparation thereof, in the presence of a chitosan-Al 2 O 3 nanocomposite film. The invention also relates to pharmaceutical compositions comprising compounds of the invention as active ingredients as well as the use of compounds of the invention for antimicrobial action.

First claim

The invention claimed is:

1. A process for preparing a compound of Formula (I):

wherein:
R 1 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl;
R 2 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl;
R 3 is H or C 1 -C 3 alkyl; and
R 4 is H, alkyl, cycloalkyl, aryl, or heteroaryl;
with the proviso that R 2 is not pyrimidinyl or triazinyl;

wherein the process comprises the following steps:
(1) dissolving chitosan in acetic acid to obtain a chitosan solution;
(2) adjusting the pH of the chitosan solution formed in step (1) above to a pH in the range of 6 to 7;
(3) adding an aqueous suspension of aluminum oxide nanoparticles portion-wise to the chitosan solution formed in step (2) above, followed by stirring to form an aqueous mixture containing the chitosan solution and aluminum oxide nanoparticles;
(4) solution casting the aqueous mixture containing chitosan and aluminum oxide nanoparticles formed in step (3) above onto a carrier substrate, followed by drying to form a chitosan-alumina nanocomposite film, wherein the chitosan-alumina nanocomposite film is a heterogeneous base catalyst;
(5) reacting a compound of Formula (III):

wherein:
R 1 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl;
R 2 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl; and
R 3 is H or C 1 -C 3 alkyl;
with the proviso that R 2 is not pyrimidinyl or triazinyl;

with a compound of Formula (IV):

wherein:
R 4 is H, alkyl, cycloalkyl, aryl, or heteroaryl;

in the presence of ethanol and the chitosan-alumina nanocomposite film formed in step (4) above [10-20 wt % based on the weight of the compound of Formula (III)], to form a reaction mixture comprising ethanol and the heterogeneous base chitosan-alumina nanocomposite film catalyst;
(6) filtering the reaction mixture formed in step (5) above to remove the heterogeneous base chitosan-alumina nanocomposite film catalyst, followed by collecting a filtrate containing ethanol;
(7) evaporating ethanol from the filtrate collected in step (6) above, to precipitate the crude compound of Formula (I) above; and
(8) recrystallizing the crude compound of Formula (I) precipitated in step (7) above from ethanol, to form the compound of Formula (I):

wherein:
R 1 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl;
R 2 is H, halogen, alkyl, cycloalkyl, aryl, or heteroaryl;
R 3 is H or C 1 -C 3 alkyl; and
R 4 is H, alkyl, cycloalkyl, aryl, or heteroaryl;
with the proviso that R 2 is not pyrimidinyl or triazinyl.

2. The process of claim 1 , wherein:
R 1 is phenyl;
R 2 is CH 3 ;
R 3 is H; and
R 4 is H.

3. The process of claim 1 , wherein the aluminum oxide nanoparticles added in step (3) have an average particle size less than 50 nm.

4. The process of claim 1 , wherein the process further comprises recycling the chitosan-alumina nanocomposite film formed in step (4), wherein the chitosan-alumina nanocomposite film is a heterogeneous base catalyst.

5. The process of claim 1 , wherein the reaction mixture formed in step (5) consists of ethanol, the compound of Formula (III), the compound of Formula (IV), and the heterogeneous base chitosan-alumina nanocomposite film catalyst.

6. The process of claim 5 , wherein the heterogeneous base chitosan-alumina nanocomposite film catalyst consists of aluminum oxide nanoparticles and chitosan.

7. The process of claim 1 , wherein the yield of the compound of Formula (I) is in the range of 90% to 95%.

Assignees

• Univ Imam Abdulrahman Bin Faisal

Inventors

• Abdel-Naby Abir Said Ibrahim
• Nabil Sara

Classifications

• B01J2235/10

  Infrared [IR] · CPC title

• B01J2235/30

  Scanning electron microscopy; Transmission electron microscopy · CPC title

• B01J2235/15

  X-ray diffraction · CPC title

• B01J35/45

  Nanoparticles · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title