ORGN 428 |
| Sitagliptin, a potent DPP-IV inhibitor, has been developing for the treatment of type II diabetes. A practical one-pot manufacturing process for the preparation of the key alpha-keto triazole amide intermediate, via a 3-component reaction, including Meldrum's acid, an amine, and a carboxylic acid, has been developed. Key to the design and development of the efficient, high-yielding process was an in-depth understanding of the mechanism of the multi-step process. The combination of online IR monitoring and chemometric analysis made it possible to profile the concentration of both the anionic and free acid forms of the Meldrum's adduct, respectively, in real time for kinetic studies, which provided a crucial tool for delineating the mechanism of this complicated reaction sequence. |
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Process R&D and Practical Syntheses of Medicinal Agents
1:00 PM-4:40 PM, Tuesday, 12 September 2006 Moscone Center -- Room 132, Oral
Division of Organic Chemistry |