Abstract
The synthesis of ras farnesyl-protein transferase inhibitor 1 is described on a multi-kilogram scale. Retrosynthetic analysis reveals chloromethylimidazole 2 and a piperazinone 3 as viable precursors. The 1,5-disubstituted imidazole system was regioselectively assembled via an improved Marckwald imidazole synthesis. A new imidazole dethionation procedure has been developed to convert the Marckwald mercaptoimidazole product to the desired imidazole. This methodology was found to be tolerant of a variety of functional groups providing good to excellent yields of 1,5-disubstituted imidazoles. A new Mitsunobu cyclization strategy was developed to prepare the arylpiperazinone fragment 3.
Original language | English (US) |
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Pages (from-to) | 229-241 |
Number of pages | 13 |
Journal | Journal of Heterocyclic Chemistry |
Volume | 40 |
Issue number | 2 |
DOIs | |
State | Published - 2003 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Organic Chemistry