Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 4: Formylation–Cyclization as a Flow–Batch Process Leads to Significant Improvements in Process Mass Intensity (PMI) and CO Generated versus the Batch–Batch Process

• Published in: Organic process research & development Vol. 24; no. 11; pp. 2478 - 2490
• Main Authors: Otte, Douglas A. L, Basu, Kallol, Jellett, Lisa, Whittington, Michael, Spencer, Glenn, Burris, Matthew, Corcoran, Emily B, Stone, Kevin, Nappi, Jarod, Arvary, Rebecca A, Donoghue, David, Ren, Hong, Maloney, Kevin M, Naber, John R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.11.2020; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Applied; Chemistry, Organic; Physical Sciences; Science & Technology; formylation; green chemistry; PMI; process mass intensity; flow chemistry; CHEMISTRY

Gefapixant citrate (MK-7264) is a P2X3 antagonist for the treatment of chronic cough. The second generation manufacturing route developed for the Step 3A/3B formylation–cyclization reaction to generate the key intermediate diaminopyrimidine (1) (AF-072) required a significant excess of ethyl formate...