A multistep continuous flow process involving (1) magnesium-halogen exchange, (2) sulfonylation with sulfuryl chloride, and (3) reaction with tert-butylamine was developed for the synthesis of an arylsulfonamide pharmaceutical intermediate in the synthesis of BMS-919373. The process was successfully implemented, including a robust control strategy to manage the levels of several process impurities, to produce 76 kg of 5-bromo-N-(tert-butyl)pyridine-3-sulfonamide (2). As the instability of the reactive intermediates and existence of strong exotherms made a batch process unsuitable for production beyond a 1 kg scale, the alternative continuous process led to a practical and robust manufacturing route to the active pharmaceutical ingredient.

• Bristol Myers Squibb
• Bristol-Myers Squibb
• Merck & Co Inc

• API

1. API
2. arylsulfonamide
3. continuous process
4. flow chemistry
5. magnesium-halogen exchange
6. manufacture of active pharmaceutical ingredient (API)
7. Research Article
8. unstable intermediates