Boeglin Damien, Bonnet Dominique, Hibert Marcel
Département de Pharmacochimie de la Communication Cellulaire, Institut Gilbert Laustriat, LC1-UMR CNRS/ULP 7175, Faculté de Pharmacie de Strasbourg, 74 route du Rhin BP24, 67401 Illkirch, Cedex, France.
J Comb Chem. 2007 May-Jun;9(3):487-500. doi: 10.1021/cc060164x. Epub 2007 Mar 15.
A convenient and reliable solid-phase strategy for the synthesis of di- and trisubstituted benzazepine derivatives was developed. 5-Amino-1-tert-butoxycarbonyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine and 5-amino-1-tert-butoxycarbonyl-7-bromo-2,3,4,5-tetrahydro-1H-benzo[b]azepine G-protein coupled receptor-targeted (GPCR-targeted) scaffolds were efficiently synthesized in a six-step solution-phase process, immobilized on the acid-labile FMPB-AM resin, and further functionalized through acylation, sulfonation, reductive amination, alkylation, and Suzuki or Buchwald-Hartwig cross-coupling reactions. The efficacy of this strategy was exemplified by the preparation of an original pilot library of di- and trisubstituted benzazepines obtained in high purity as assessed by both 1H NMR and liquid chromatography/mass spectrometry (LC/MS) analysis.
开发了一种用于合成二取代和三取代苯并氮杂卓衍生物的便捷可靠的固相策略。5-氨基-1-叔丁氧羰基-2,3,4,5-四氢-1H-苯并[b]氮杂卓和5-氨基-1-叔丁氧羰基-7-溴-2,3,4,5-四氢-1H-苯并[b]氮杂卓G蛋白偶联受体靶向（GPCR靶向）支架通过六步溶液相过程高效合成，固定在酸不稳定的FMPB-AM树脂上，并通过酰化、磺化、还原胺化、烷基化以及铃木或布赫瓦尔德-哈特维希交叉偶联反应进一步官能化。通过制备一个原始的二取代和三取代苯并氮杂卓先导库证明了该策略的有效性，通过1H NMR和液相色谱/质谱（LC/MS）分析评估，该先导库具有高纯度。
