Scale-Up of Trisodium [(3β,5β,12α)-3-[[4(<i>S</i>)-4-[Bis[2-[bis[(carboxy-<i>kO</i>)methyl]amino-<i>kN</i>]ethyl]amino-<i>kN</i>]-4-(carboxy-<i>kO</i>)-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)], a Gd(III) Complex under Development As a Contrast Agent for MRI Coronary Angiography

Abstract

Process chemistry involved in the discovery and development routes to trisodium [(3β,5β,12α)-3-[[4( S )-4-[bis[2-[bis[(carboxy- kO )methyl]amino- kN ]ethyl]amino- kN ]-4-(carboxy- kO )-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)] ( B22956/1 ) starting from l -glutamic acid and (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid is described. The best process is based on seven chemical steps and overcomes difficult purification protocols. Such process has been successfully implemented to prepare multikilogram batches of the target compound in 20% overall yield from (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid.