Promotion of Water As Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles Under Acidic Conditions

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Apr 1

PMID 38559978

Authors

Shuhei Yasuda

Hanne Svergja

Cecilie Elisabeth Olsen

Bard Helge Hoff

Affiliations

Soon will be listed here.

Abstract

A switch of reaction medium from organic solvents to water can improve the safety and lower the cost of production processes. Hydrochloric acid-promoted amination of fused pyrimidines has been studied using 4-chloro-7-pyrrolo[2,3-]pyrimidine and aniline as model compounds. Higher rate was observed in water than in four alcoholic solvents and DMF. An important aspect is that the amount of acid should be kept low to minimize the competing solvolysis. The substrate scope for the amination in water was evaluated by reacting 4-chloro-7-pyrrolo[2,3-pyrimidine with 20 aniline derivatives with variance in steric and electronic properties. Preparative useful reactions were seen for 14 of the 20 derivatives. Unsuited nucleophiles are -substituted anilines with a p below 1. Amination of the corresponding quinazoline, thienopyrimidine, and purine also proceeded well in water. Highly lipophilic and crystalline compounds are more efficiently aminated in 2-propanol. Aliphatic and benzylic amines react poorly under acidic conditions, but these aminations can be done in water without acid.

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