Scale-Up of 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-)], a Gd(III) Complex under Development As a Contrast Agent for MRI Coronary Angiography

Anelli, Pier Lucio; Brocchetta, Marino; Lattuada, Luciano; Manfredi, Giuseppe; Morosini, Pierfrancesco; Murru, Marcella; Palano, Daniela; Sipioni, Marco; Visigalli, Massimo

doi:10.1021/op900008a.s001

Scale-Up of 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-)], a Gd(III) Complex under Development As a Contrast Agent for MRI Coronary Angiography

journal contribution

posted on 2009-07-17, 00:00 authored by Pier Lucio Anelli, Marino Brocchetta, Luciano Lattuada, Giuseppe Manfredi, Pierfrancesco Morosini, Marcella Murru, Daniela Palano, Marco Sipioni, Massimo Visigalli

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.