5-Iodo-3-Ethoxypyrazoles: An Entry Point to New Chemical Entities

✍ Scribed by Sandrine Guillou; Yves L. Janin

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 305 KB
• Volume: 16
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200903442

✦ Synopsis

Abstract

Our program, which has focused on the preparation of new pyrazole derivatives, has led us to report here an original and simplified preparation of ethyl 3‐ethoxy‐1__H__‐pyrazole‐4‐carboxylate. This is based on the reaction of hydrazine monohydrochloride and diethyl 2‐(ethoxymethylene)malonate. Further transformations of this key compound allowed the preparation of the two possible iodinated isomers, namely, 3‐ethoxy‐4‐iodo‐ and 3‐ethoxy‐5‐iodo‐1__H__‐pyrazole. These compounds have opened the way to a quick access to many original pyrazole series. As an illustration, we report here on the selectivity of N‐arylation, by using the Lam and Cham method, the C4‐ and C5‐arylation of some of these 3‐ethoxypyrazole derivatives by using the Suzuki–Miyaura reaction, and C5‐benzylation reactions by means of the Negishi reaction. This was followed by hydrolysis of the ethoxy group, which led to the corresponding pyrazol‐3‐one derivatives. As a conclusion of this work, we conducted an investigation into the regiochemistry of the condensation between diethyl 2‐(ethoxymethylene)malonate and the hydrochloride salts of methyl, benzyl, or phenyl hydrazine.