Synthesis of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP)

✍ Scribed by Chuansheng Niu; Jun Li; Terrence W. Doyle; Shu-Hui Chen

• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 603 KB
• Volume: 54
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(98)00328-7

✦ Synopsis

Palladium-catalyzed cross-coupling of methylboronic acid with 2-chloro-3-nitropyridine produced 2methyl-3-nitropyridine 4 in one step in high yield. Oxidation of 4 with selenium dioxide gave aldehyde 5. Alternatively, condensation of 4 with DMFDMA followed by oxidation gave 5 in a two step higher yielding conversion. Subsequent direct coupling of 5 with thiosemicarbazide followed by reduction of the nitro group using stannous chloride or sodium sulfide provided 3-AP (3). Reduction with sodium hydrosulfite gave 3-HAP (8). Finally a route which avoids the reduction of a nitro function was devised. Thus direct coupling of styrene with 2-chloro-3-aminopyridine 9 under Heck reaction conditions gave 16 which was converted to 17, oxidized to the aldehyde 18 and converted to 3-AP (3) with in situ deblocking of the t-Boc functionality.