The Chemical Development of the Commercial Route to Sildenafil: A Case History

This paper is a case history of the chemical development of sildenafil which covers various aspects of work in chemical development namely:  route selection, scale-up issues, the development of an efficient synthesis with high throughput, process safety, and environmental issues. Interesting chemical points include improved methods of preparing pyrazolo[4,3-d]pyrimidines and the unusual isolation of an intermediate as its double salt (10). The potential dangers of nitrating pyrazole-5-carboxylic acids which are activated to a decarboxylation reaction are discussed.