Details

Autor(en) / Beteiligte

• Graham, Mark A
• Raw, Steven A
• Andrews, David M
• Good, Catherine J
• Matusiak, Zbigniew S
• Maybury, Mark
• Stokes, Elaine S. E
• Turner, Andrew T

Titel

Flexible and Scalable Route to HDAc Inhibitors Containing an Unusual Trisubstituted Pyridine Core

Ist Teil von

• Organic process research & development, 2012-07, Vol.16 (7), p.1283-1292

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2012

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A scalable route to histone deacetylase inhibitors containing an unusual 2-aryl-3-cyano-5-aminomethylpyridine core has been developed which has the flexibility to deliver a range of compounds on at least a multigram scale. The key step involves a novel Mannich reaction using 3-dimethylaminoacrolein, formaldehyde, and a secondary amine to yield a 2-(alkylaminomethyl)-3-dimethylaminoacrolein. Tuning of this reaction in process development was fundamental to the success of the approach in terms of flexibility and operability on scale-up. This new methodology will also enable access an underutilised family of 3,5-disubstituted pyrid-2-ones and 2,3,5-trisubstituted pyridines.