A Simple Synthesis of 5-(2-Aminophenyl)-1H-pyrazoles

✍ Scribed by Monika Janjić; Rok Prebil; Uroš Grošelj; David Kralj; Črt Malavašič; Amalija Golobič; Katarina Stare; Georg Dahmann; Branko Stanovnik; Jurij Svete

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: German
• Weight: 335 KB
• Volume: 94
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.201100055

✦ Synopsis

Abstract

A four‐step synthesis of 1‐substituted 5‐(2‐aminophenyl)‐1__H__‐pyrazoles 5 as a novel type of histamine analogs and versatile building blocks for further transformations was developed. The synthesis starts from commercially available 2‐nitroacetophenone (12), which is converted into the enamino ketone 13 as the key intermediate. Cyclization of the key intermediate 13 with monosubstituted hydrazines 14a–14l afforded the 5‐(2‐nitrophenyl)‐1__H__‐pyrazoles 17a–17l. Finally, catalytic hydrogenation of the nitro compounds 17a, 17c–17e, and 17g–17j furnished the title compounds 5a, 5c–5e, and 5g–5j, respectively, in good yields. As demonstrated by some further transformations, additional functionalization of compounds 17 and 5 is feasible, either by electrophilic substitution at C(4) of the pyrazole ring, or at the NH~2~ group.