Multi-step Split Synthesis on the TridentTM: Parallel Solution-Phase Synthesis of Urea and Amide Library

The Trident automated synthesizer was successfully employed in a two-step split synthesis of amides, sulfonamides and ureas. The key synthetic step involved the preparation of 24 secondary amines from 4 primary amines and 6 carbonyl compounds using Ti(OiPr)4 and NaBH4. These amines were then used in 192 reactions to synthesize 96 ureas in duplicate and 96 reactions to synthesize 48 amides and 48 sulfonamides. The reaction sequences clearly demonstrate the Trident's ability to perform parallel solution phase synthesis and to handle air-sensitive reagents such as Ti(OiPr)4, alkyl isocyanates, acid chlorides and aryl sulfonyl chlorides.