US 2026/0257997 A1 · A METHOD FOR SYNTHESIZING ARYL ETHERS ORTHO-SUBSTITUTED TO THE NITROGEN ATOM OF N-HETEROCYCLES

Abstract

The present invention pertains to the technical field of synthesis and application of novel compounds, and discloses a synthesis method for aryl ethers substituted ortho to nitrogen in nitrogen-containing heterocycles. Under the catalysis of hexamethylphosphoramide (HMPA), using N,N-diisopropylethylamine (DIEA) as a base and with the assistance of POBr3, the method employs nitrogen oxides to react with phenols, thereby achieving ortho-aryloxy substitution on nitrogen heterocycles. The method of the invention exhibits excellent atom economy (3a, 96%), green solvent selection (using ethyl acetate as solvent), mild reaction conditions, short reaction times (most substrates react within 5 minutes), broad substrate scope, and inexpensive and readily available starting materials. This method provides a convenient, efficient, green, and practical approach for synthesizing 1-aryloxyisoquinolines, 2-aryloxyquinolines, and 2-aryloxypyridine compounds.

Claims9

Dependent claims

A method for synthesizing an aryl ether ortho-substituted to the nitrogen atom of an N-heterocycle, characterized by:

reacting an N-heterocyclic N-oxide with a phenol using hexamethylphosphoramide (HMPA) as a catalyst, N,N-diisopropylethylamine (DIEA) as a base, and POBr3 as an auxiliary agent, thereby effecting ortho-aryloxy substitution relative to the nitrogen atom of an N-heterocycle;
wherein said aryl ether is an aryl heteroaryl ether synthesized according to the following route:
the method comprises reacting a compound of N-heterocyclic N-oxide 1 with a phenol in ethyl acetate (EA) solvent, using N,N-diisopropylethylamine (DIEA) as a base, hexamethylphosphoramide (HMPA) as a catalyst, and POBr3 as an auxiliary agent, to yield compound 3;
wherein R1 is selected from the group consisting of C1-C6 alkyl, halogen, C1-C6 ester, phenyl, and phenylethynyl;
and R2 is selected from the group consisting of C1-C6 alkyl, C1-C6 alkenyl, cyano, C1-C6 alkoxy, and halogen.

2 more elements

Dependencies are inferred from the claim text.

A method for synthesizing aryl ethers ortho-substituted to the nitrogen atom of n-heterocycles

Life of this patent

A method for synthesizing aryl ethers ortho-substituted to the nitrogen atom of n-heterocycles

Life of this patent

Abstract

Claims9