Imidazo[1,2-A]pyridine-3-carboxylate derivative and preparation method thereof

Patent metadata

Field	Value
Publication number	US-10323033-B2
Application number	US-201816004188-A
Country	US
Kind code	B2
Filing date	Jun 8, 2018
Priority date	Jun 8, 2017
Publication date	Jun 18, 2019
Grant date	Jun 18, 2019

Abstract

Provided are an imidazo[1,2-a]pyridine-3-carboxylate derivative and a preparation method thereof, and more particularly, a method of effectively preparing an imidazo[1,2-a]pyridine-3-carboxylate derivative by performing an aza-[3+2] cycloaddition reaction of a pyridine derivative with an α-diazo oxime ether derivative in the presence of a copper (II) catalyst, and an imidazo[1,2-a]pyridine-3-carboxylate derivative prepared thereby.

First claim

What is claimed is:

1. A preparation method of an imidazo[1,2-a]pyridine-3-carboxylate derivative comprising:
performing an aza-[3+2] cycloaddition reaction of a pyridine derivative represented by Chemical Formula 6 below with an α-diazo oxime ether derivative represented by Chemical Formula 7 below in the presence of a copper (II) catalyst, thereby preparing an imidazo[1,2-a]pyridine-3-carboxylate derivative represented by Chemical Formula 1 below:

in Chemical Formulas 1, 6, and 7,
R 1 is (C1-C10)alkyl, (C6-C12)aryl or (C3-C12)heteroaryl, and the aryl of R 1 may be further substituted with one or more selected from the group consisting of (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, halogen, nitro, (C1-C10)alkylcarbonyl, (C1-C10)alkoxycarbonyl and (C6-C12)aryloxy;
R 2 is (C1-C10)alkyl or halo(C1-C10)alkyl;
R 3 is (C1-C10)alkoxy;
X is CR b or N;
Y is CR c or N;
Z is CR d or N;
R a to R d are each independently hydrogen, (C1-C10)alkyl, halo(C1-C10)alkyl, halogen, (C1-C10)alkylcarbonyl, halo(C1-C10)alkylcarbonyl, (C1-C10)alkoxycarbonyl, halo(C1-C10)alkoxycarbonyl, (C6-C12)aryl(C1-C10)alkyloxy, (C6-C12)aryl or (C3-C12)heteroaryl, or may be linked to an adjacent substituent via —CR 11 ═CR 12 —CR 13 ═CR 14 — to form a fused ring, and the aryl of R a to R d may be further substituted with one or more selected from (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, (C6-C12)aryl and halogen;
R 11 to R 14 are each independently hydrogen, (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, (C6-C12)aryl, or halogen; and
the heteroaryl includes one to four heteroatoms selected from N, O and S.

2. The preparation method of claim 1 , wherein the copper (II) catalyst is one or two or more selected from the group consisting of Cu(OAc) 2 [Copper(II) acetate], Cu(OTf) 2 [Copper(II) triflate], Cu(acac) 2 [Copper(II) acetylacetonate], Cu(tfacac) 2 [Copper(II) trifluoroacetylacetonate] and Cu(hfacac) 2 [Copper(II) hexafluoroacetylacetonate].

3. The preparation method of claim 1 , wherein the α-diazo oxime ether derivative represented by Chemical Formula 7 is used in an amount of 1 to 3 equivalents with respect to the pyridine derivative represented by Chemical Formula 6.

4. The preparation method of claim 1 , wherein the copper (II) catalyst is used in an amount of 1 to 20 mol % with respect to the pyridine derivative represented by Chemical Formula 6.

5. The preparation method of claim 1 , wherein the reaction is performed in the presence of one or two or more organic solvents selected from trifluoroethanol, 1,4-dioxane, acetonitrile, toluene, tetrahydrofuran, dimethylformamide, dichloromethane, dichloroethane, N,N-dimethylformamide, hexane, benzene, xylene, chlorobenzene, hexafluorobenzene, octafluorotoluene, tetrabutylalcohol, methanol and ethanol.

6. A preparation method of an imidazo[1,2-a]pyridine-3-carboxylate derivative comprising:
performing an aza-[3+2] cycloaddition reaction of a pyridine derivative represented by Chemical Formula 6A below with an α-diazo oxime ether derivative represented by Chemical Formula 7A below in the presence of a copper (II) catalyst in trifluoroethanol, followed by transesterification with trifluoroethanol as a solvent, thereby preparing an imidazo[1,2-a]pyridine-3-carboxylate derivative represented by Chemical Formula 1A below:

in Chemical Formulas 1A, 6A, and 7A,
R 1 is (C1-C10)alkyl or (C6-C12)aryl, and the aryl of R 1 may be further substituted with one or more selected from the group consisting of (C1-C10)alkyl, (C1-C10)alkoxy, halogen, nitro and (C1-C10)alkoxycarbonyl;
R 2 is (C1-C10)alkyl;
Y is CR c or N;
R 3 is (C1-C10)alkoxy;
R a is hydrogen, (C1-C10)alkyl or (C6-C12)aryl(C1-C10)alkyloxy;
R b is (C1-C10)alkyl or (C6-C12)aryl, and the aryl of R b may be further substituted with one or more selected from (C1-C10)alkyl and halogen; and
R c is hydrogen or (C1-C10)alkyl.

7. The preparation method of claim 6 , wherein the copper (II) catalyst is one or two or more selected from the group consisting of Cu(OAc) 2 [Copper(II) acetate], Cu(OTf) 2 [Copper(II) triflate], Cu(acac) 2 [Copper(II) acetylacetonate], Cu(tfacac) 2 [Copper(II) trifluoroacetylacetonate], and Cu(hfacac) 2 [Copper(II) hexafluoroacetylacetonate].

8. The preparation method of claim 6 , wherein the α-diazo oxime ether derivative represented by Chemical Formula 7A is used in an amount of 1 to 3 equivalents with respect to the pyridine derivative represented by Chemical Formula 6A.

9. The preparation method of claim 6 , wherein the copper (II) catalyst is used in an amount of 1 to 20 mol % with respect to the pyridine derivative represented by Chemical Formula 6A.

Assignees

• Knu Industry Cooperation Found

Inventors

• Lee Phil Ho

Classifications

• B01J2531/16

  Copper · CPC title

• B01J31/0227

  being perfluorinated, i.e. comprising at least one perfluorinated moiety as substructure in case of polyfunctional compounds · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/36

  Compounds containing methylenedioxyphenyl groups, e.g. sesamin · CPC title