71700-44-2Relevant articles and documents
An Efficient and Cost-Effective Synthesis of Pagoclone
Stuk, Timothy L.,Assink, Bryce K.,Bates Jr., Ronald C.,Erdman, David T.,Fedij, Victor,Jennings, Sandra M.,Lassig, Jennifer A.,Smith, Randy J.,Smith, Traci L.
, p. 851 - 855 (2013/09/05)
The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2- oxohexyl)-l-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABAA receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a β-keto phosphonium salt was prepared by selectively reacting a primary α-bromo ketone with triphenylphosphine in the presence of a secondary α-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a γ-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.
Regioselective syntheses of 2-amino-4,5-dialkylthiophene-3-carboxylates and their conversion to 3,4-dihydro-4-oxothieno[2,3-d]pyrimidine-2-carboxylates
Madding,Thompson
, p. 581 - 587 (2007/10/02)
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