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

被引：12

作者：

Anelli, Pier Lucio ^{[1
]}

Brocchetta, Marino ^{[1
]}

Lattuada, Luciano ^{[1
]}

Manfredi, Giuseppe ^{[1
]}

Morosini, Pierfrancesco ^{[1
]}

Murru, Marcella ^{[1
]}

Palano, Daniela ^{[1
]}

Sipioni, Marco ^{[1
]}

Visigalli, Massimo ^{[1
]}

机构：

[1] Bracco Imaging Spa, Ctr Ric Bracco, I-10010 Colleretto Giacosa, TO, Italy

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2009年 / 13卷 / 04期

关键词：

GLUTAMIC-ACID; AMINO-ACIDS; ESTERS; MITSUNOBU; DERIVATIVES; PROTECTION; GADOLINIUM; B22956/1; LACTAMS; AMIDES;

D O I：

10.1021/op900008a

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Process chemistry involved in the discovery and development routes to trisodium [(3 beta,5 beta,12(alpha)-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 (3 alpha,5 beta,12 alpha)-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 (3 alpha,5 beta,12 alpha)-3,12-dihydroxycholan-24-oic acid.

引用

页码：739 / 746

页数：8