Reiterative Chiral Resolution/Racemization/Recycle (RRR Synthesis) for an Effective and Scalable Process for the Enantioselective Synthesis of a Dual IDO1/TDO2 Inhibitor Imidazoisoindole Derivative

被引：3

作者：

Crescenzi, Cristina ^{[1
]}

Fuchss, Thomas ^{[2
]}

Ippoliti, Dimitri ^{[1
]}

Langella, Annunziata ^{[1
]}

Di Mola, Antonia ^{[3
]}

Massa, Antonio ^{[3
]}

Rozzi, Diego ^{[1
]}

机构：

[1] Merck Serono SpA, I-00012 Guidonia Montecelio, RM, Italy

[2] Merck Healthcare KGaA, D-64293 Darmstadt, Germany

[3] Univ Salerno, Dipartimento Chim & Biol A Zambelli, I-84084 Fisciano, SA, Italy

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2020年 / 24卷 / 06期

关键词：

anticancer; heterocycles; 5H-imidazo[5,1-a]isoindole; asymmetric synthesis; chiral resolution; INDOLEAMINE 2,3-DIOXYGENASE; IMIDAZOLEISOINDOLE DERIVATIVES; IDO1; INDOLEAMINE-2,3-DIOXYGENASE; RESOLUTION; CATALYSIS; DESIGN;

D O I：

10.1021/acs.oprd.0c00004

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Herein, we report an effective and scalable highly enantioselective synthesis of an 5H-imidazo[5,1-a]isoindole derivative via an RRR-synthesis approach (resolution-racemization-recycle). Chiral resolution performed with the aid of 2,3-dibenzoyl-D-tartaric acid allowed the obtaining of the desired enantiomer in high enantiopurity (>99% ee) and good yield. The undesired enantiomer was subjected to racemization under basic conditions and again to resolution, improving the efficiency of the entire process. The asymmetric formation of the new stereocenter in an early stage of the synthesis scheme was also investigated by means of organocatalytic systems.

引用

页码：1018 / 1023

页数：6

共 9 条

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