Search

CN-121974859-A - Preparation method of 6-iodoquinazoline compound

CN121974859ACN 121974859 ACN121974859 ACN 121974859ACN-121974859-A

Abstract

The invention discloses a preparation method of 6-iodoquinazoline compounds, which belongs to the technical field of organic synthesis, the invention takes o-amino aryl ketone and aldehyde compounds as raw materials, in a solvent, under the action of an iodination reagent and an amination reagent, a one-pot method is adopted to react to obtain the 6-iodoquinazoline compound of the formula 3. The synthesis method of the 6-iodoquinazoline compound provided by the invention does not need a catalyst, an additive, alkali and an additional oxidant, and can be used for constructing the target 6-iodoquinazoline compound by four-component reaction in a single step. The synthesis method provided by the invention has the remarkable characteristics of low cost, simple process and environment-friendly idea, can be used for amplification experiments, and has unique advantages and application potential in the chemical synthesis field. The synthesis method of the 6-iodoquinazoline compound has wide substrate applicability and excellent functional group compatibility.

Inventors

  • WU JIWEI
  • CHEN HOULIN
  • ZHOU HUIQIAO
  • MEI RUI
  • LIU ZIKUN
  • Lv Zhiye

Assignees

  • 安徽科技学院

Dates

Publication Date
20260505
Application Date
20260320

Claims (8)

  1. 1. The preparation method of the 6-iodoquinazoline compound is characterized by comprising the following steps of: In an air atmosphere, taking o-amino aryl ketone of formula 1 and aldehyde compound of formula 2 as raw materials, and reacting in a solvent under the action of an iodination reagent and an amination reagent to obtain a 6-iodoquinazoline compound of formula 3, wherein the synthetic route is as follows: ; wherein R 1 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkyl or substituted alkyl, and R 2 is selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl.
  2. 2. The preparation method of the 6-iodoquinazoline compound according to claim 1, wherein R 1 is selected from phenyl, substituted phenyl, thienyl, C1-C3 linear alkyl or C3-C6 branched alkyl, and R 2 is selected from phenyl, substituted phenyl, thienyl, C1-C3 linear alkyl or C3-C6 branched alkyl.
  3. 3. The method for producing a 6-iodoquinazoline compound according to claim 2, wherein the substituent of the substituted phenyl group is a C1 to C3 alkyl group, a methoxy group, a halogen atom or a cyano group, and the branched alkyl group of C3 to C6 is a t-butyl group.
  4. 4. The method for preparing 6-iodoquinazoline compounds according to claim 1, wherein the iodination reagent is N-iodosuccinimide and/or I 2 .
  5. 5. The method for producing 6-iodoquinazoline according to claim 1, wherein the amination reagent is at least one of ammonia water, ammonium chloride, ammonium bromide, ammonium iodide, ammonium acetate and ammonium phosphate.
  6. 6. The method for producing 6-iodoquinazoline compounds according to claim 1, wherein the molar ratio of the o-aminoaryl ketone of formula 1 to the aldehyde compound of formula 2 is 1:2 to 4, the molar ratio of the o-aminoaryl ketone of formula 1 to the iodinating agent is 1:3 to 6, and the molar ratio of the o-aminoaryl ketone of formula 1 to the aminating agent is 1:1 to 4.
  7. 7. The method for producing 6-iodoquinazoline according to claim 1, wherein the solvent is dimethyl sulfoxide, N-dimethylformamide, acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, toluene or chlorobenzene.
  8. 8. The method for preparing the 6-iodoquinazoline compound according to claim 1, wherein the reaction is carried out at 60-120 ℃ for 6-24 hours.

Description

Preparation method of 6-iodoquinazoline compound Technical Field The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 6-iodoquinazoline compound. Background Quinazoline compounds are a class of nitrogen-containing heterocyclic structures of great value, are widely present in natural products and drug molecules, and exhibit a variety of biological activities including antibacterial, anti-inflammatory, antimalarial, anticonvulsant and antitumor. Currently, a variety of drugs containing quinazoline frameworks have been used clinically, such as Prazosin for the treatment of hypertension and anxiety, and as antitumor drugs Lapatinib and Gefitinib as small molecule kinase inhibitors. In recent years, various methods have been developed for the synthesis of quinazoline compounds, however, the methods depend on metal catalysts or excessive oxidants, and have certain limitations in the application of pharmaceutical synthesis. The organic iodine compound is taken as an important functional molecule, widely exists in natural products, is a key synthesis intermediate, has important application in the fields of preparation of organic metal reagents, free radical reaction, nucleophilic substitution, cross coupling and the like, and becomes an important structural unit in total synthesis, pharmaceutical chemistry and material science. Iodine atoms are introduced into a quinazoline system, so that new possibilities are provided for structural modification and conversion of the medicaments. However, the current methods for direct synthesis of 6-iodoquinazoline compounds are limited. In the prior art, the decarboxylation cyclization reaction of 2-amino-5-iodobenzophenone and glycine is realized through electrochemical oxidation, so that a 6-iodoquinazoline structure is constructed. However, the method relies on pre-prepared iodinated raw materials, the steps are complicated, and the application range of the substrate is narrow. Disclosure of Invention The invention provides a preparation method of a 6-iodoquinazoline compound, and aims to solve the problems that the existing synthesis method of the 6-iodoquinazoline compound is narrow in substrate application range, complex in synthesis steps and depends on iodized raw materials. The invention takes the o-amino aryl ketone and the aldehyde as raw materials, can obtain the target product in one step through one-pot reaction, does not need a catalyst or an external oxidant, and has the advantages of easily available raw materials, simple process and wide substrate range. The preparation method provided by the invention has the advantages of high chemical selectivity, good yield and excellent tolerance to various functional groups. The invention aims to provide a preparation method of a 6-iodoquinazoline compound, which comprises the following steps: In an air atmosphere, taking o-amino aryl ketone of formula 1 and aldehyde compound of formula 2 as raw materials, and reacting in a solvent under the action of an iodination reagent and an amination reagent to obtain a 6-iodoquinazoline compound of formula 3, wherein the synthetic route is as follows: Wherein R 1 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkyl, or substituted alkyl, and R 2 is selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl. As a preferred embodiment, R 1 is selected from phenyl, substituted phenyl, thienyl, C1-C3 linear alkyl or C3-C6 branched alkyl, and R 2 is selected from phenyl, substituted phenyl, thienyl, C1-C3 linear alkyl or C3-C6 branched alkyl. As a preferred embodiment, the substituent of the substituted phenyl is a C1-C3 alkyl group, a methoxy group, a halogen atom or a cyano group, and the branched alkyl group of C3-C6 is a tert-butyl group. As a preferred embodiment, the iodinating agent is N-iodosuccinimide (NIS) and/or I 2. As a preferred embodiment, the amination reagent is at least one of ammonia, ammonium chloride, ammonium bromide, ammonium iodide, ammonium acetate and ammonium phosphate. As a preferred embodiment, the molar ratio of the o-aminoaryl ketone of the formula 1 to the aldehyde compound of the formula 2 is 1:2-4, the molar ratio of the o-aminoaryl ketone of the formula 1 to the iodinating agent is 1:3-6, and the molar ratio of the o-aminoaryl ketone of the formula 1 to the aminating agent is 1:1-4. As a preferred embodiment, the solvent is dimethyl sulfoxide, N-dimethylformamide, acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, toluene or chlorobenzene. As a preferred embodiment, the reaction is specifically carried out at 60-120 ℃ for 6-24 hours. As a preferred embodiment, after the reaction is finished, adding water into a reaction system, extracting by adopting ethyl acetate to obtain an organic layer, drying the organic layer by adopting anhydrous magnesium sulfate, filtering to obtain an organic phase, adding silica gel p