1584154-98-2Relevant articles and documents
Chiral resolution and serendipitous fluorination reaction for the selective dopamine d3 receptor antagonist BAK2-66
Kumar, Vivek,Banala, Ashwini K.,Garcia, Erick G.,Cao, Jianjing,Keck, Thomas M.,Bonifazi, Alessandro,Deschamps, Jeffery R.,Newman, Amy Hauck
, p. 647 - 651 (2014/07/07)
The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)1H- indole-2-carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutyl-product (8). This article not subject to U.S. Copyright. Published 2014 by the American Chemical Society.
