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DOI: 10.1055/s-2004-825625
Two Concise Syntheses of Cialis via the N-Acyliminium Pictet-Spengler Reaction
Publication History
Publication Date:
08 June 2004 (online)
Abstract
The imine derived from piperonal and d-tryptophan methyl ester underwent N-acyliminium Pictet-Spengler reaction with either Fmoc-sarcosyl chloride or chloroacetyl chloride. The products were readily converted to the drug Cialis.
Key words
imine acylations - Pictet-Spengler reactions - indoles - diketopiperazines - drugs
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References
Note added in proof
The large-scale process for Lilly’s synthesis of Cialis has now appeared in the patent literature (Chelius, E. C.; Martinelli, M. J.; Pawlak, J. M.; Orme, M. W.; Doecke, C. W.; WO patent 011463, 2004). By carrying out the acid-catalyzed Pictet-Spengler reaction in an appropriate solvent where the cis diastereomer 1 is less soluble than the trans diastereomer 2, a nearly quantitative yield of 1 is elegantly obtained.