Synthesis of N¹,N³-bis(2,3-dihydroxypropyl)-5-nitroisophthalamide

摘要

The present disclosure generally relates to a new process for the preparation of high purity 5-nitro-isophthalamide compounds, which are useful as intermediates for the preparation of imaging agents, such as iodinated x-ray contrast imaging agents like ioversol, iohexyl and iopamidol.

主权项

1. A process for preparing a diamide compound of formula (2), the process comprising:
(i) forming a reaction mixture comprising a diester of formula (1), a primary amine of formula RNH.sub.2, a basic catalyst and a solvent; and (ii) heating the reaction mixture to a reaction temperature of from about 25° C. to less than 65° C. and holding the reaction mixture at the reaction temperature for a reaction time sufficient to generate a reaction product mixture comprising diamide compound formula (2) wherein,
R, R1 and R2 independently selected from C1 to C18 straight or branched chain hydrocarbyl or substituted hydrocarbyl, andthe molar ratio of the primary amine to the diester is from 2:1 to about 2.4:1;wherein the reaction product mixture comprises the diamide of formula (2) and at least one of the diester of formula (1), an acid amide of formula (3), an amide ester of formula (4) or an amide ester of formula (5) wherein the wherein the content of the acid amide of formula (3) is about 2% or or less, by weight of the sum of the content of formulae (1) through (5).