Sharon D. Boggs, Jeremy D. Cobb, K. Gudmundsson
Feb 14, 2007
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0
Influential Citations
39
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Journal
Organic Process Research & Development
Abstract
An efficient asymmetric synthesis of N-[(1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl]-2-pyridinecarboxamide 1, a potential treatment for human papillomavirus infections, is described. The key step in the synthesis of this molecule is an asymmetric reductive amination directed by chiral (phenyl)ethylamines resulting in up to 96% disastereo facial selectivity. The synthesis is also highlighted by isolation of a unique 2-picolinic acid salt of (1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-amine (13). Subsequent application of 1-propylphosphonic acid cyclic anhydride (T3P) for convenient amide formation from the two components of the salt provides the product 1 in high yield. The process research work leading to the final synthesis includes a racemic synthesis followed by resolution with chiral supercritical fluid chromatography, and an enantioselective reductive amination via chiral transfer hydrogenation catalyzed by Ru(II) complexes of N-[(1S,2S)-2-amino-1,2-diphenylethyl]-1-naphthalenesulfonamide or...