A Rapid and Efficient Synthesis of 2-Butyl-5-Chloro-3H-Imidazole-4-Carboxaldehyde

Abstract

A rapid, efficient, cost effective procedure has been developed for the synthesis of 2-butyl-5-chloro-3H-imidazole-4-carboxaldehyde. Preparation of methyl pentanimidate was accomplished in just 12 hours, followed by a sequence of reactions without isolation and purification of the formed intermediates. The final compound was purified by simple acid-base treatment to get a product with 99.9% HPLC purity.

Key words

imidazole - imidates - Vilsmeier reagents - nitrile - tetrazole

References

• 1 Duncia JV. Carini DJ. Chiu AT. Pierce ME. Smith RD. Wells GJ. Wang PC. Wexier PR. Johnson AL. Timmermans PBMWM. Drugs Fut.  1991,  16:  305 
• 2 Carini DJ. Duncia JV. Aldrich PE. Chiu AT. Johnson AL. Pierce ME. Price WA. Santella JB. Wells GJ. Wexler RR. Wong PC. Yoo SE. Timmermans PBMWM. J. Med. Chem.  1991,  34:  2525 ; and references reported therein
• 3 Scrip  1994,  1963:  23 
• 4 Takeda Chemical Industries Ltd. . inventors; JP  5798270.  ; Chem. Abstr. 1983, 98, 4543a
• 5 Yamamoto T, Hibi Y, and Ogawa T. inventors; US Patent  5395943. 
• 6 Elz S. Kramer K. Pertz HH. Detert H. Laak AK. Kuhne R. Schunack W. J. Med. Chem.  2000,  43:  1073 
• 7 Furukawa Y, Kishimoto S, and Nishikawa K. inventors; US Patent  4355040. 
• 8 Basappa MPS. Mantelingu K. Swamy SN. Rangappa KS. Bioorg. Med. Chem.  2003,  11:  4539 
• 9 Pardhasaradhi M, Srinivas K, and Snehalatha Nair CK. inventors; US patent  6326498.  ; Chem. Abstr. 2001, 136, 5996
• 10 Srinivas K. Snehalatha Nair CK. Ramesh S. Pardhasaradhi M. Org. Prep. Proced. Int.  2003,  35:  537 
• 11 Dzurion P. Schunarck W. Arch. Phamazie  1974,  307:  470 
• 12 Shi Y.-J. Frey LF. Tschaeu DM. Verhoeven TR. Synth. Commun.  1993,  23:  2623 
• 13 Griffiths GJ. Chimia  1997,  51:  283 
• 14 Griffiths GJ. Hauck MB. Imwinkelried R. Kohr J. Roten C. Stucky GC. J. Org. Chem.  1999,  64:  8084 
• 15 Pardhasaradhi M, Srinivas K, Snehalatha Nair CK, and Ramesh S. inventors; Indian Patent  NF132.