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oai:figshare.com:article/34046531 2026-10-01T15:12:34Z category_1 category_7 category_13 category_14 category_21 category_272 category_734 category_61 category_135 portal_63 item_type_6 month_year_10_2026

Telescoped Two-Step Continuous-Flow Synthesis of Nevirapine Enabled by the On-Demand Generation of NaHMDS Maksim Vasilev (16942307) Rajasekar Reddy Annapureddy (4394425) Chengfeng Ye (2454577) Sridhar Regati (3332055) Praveen Kumar Gajula (2420815) Jonathan Bietsch (9755837) Zhirui Wang (629192) Jack D. Brown (2726944) Gopal Sirasani (1348278) Aravind S. Gangu (16942310) Paul Guo (25157114) Bo Qu (150402) Chris H. Senanayake (1392808) Biophysics Medicine Genetics Molecular Biology Biotechnology Environmental Sciences not elsewhere classified Biological Sciences not elsewhere classified Developmental Biology Computational Biology key therapeutic agent enables direct conversion bed column reactor ∼ 365 g total residence time nevirapine without isolation delivers crude nevirapine step fully continuous purity ), providing optimized process operates current commercial synthesis demand continuous generation demand generated nahmds step continuous demand generation viramune ), hplc purity time yield nevirapine enabled first time ∼ 2 trade name telescoped two sodium packed sodium bis reaction stages process employs nah applied friendly base flow synthesis flow process effective alternative cyclization intermediate 10 min 1 infection A telescoped two-step fully continuous-flow process for the synthesis of nevirapine (trade name: Viramune), a key therapeutic agent for the prevention and treatment of HIV-1 infection, has been developed. The process employs, for the first time, sodium bis(trimethylsilyl)amide (NaHMDS) as a homogeneous, process-friendly base for both reaction stages and enables direct conversion of methyl 2-(cyclopropylamino)nicotinate and 2-chloro-3-amino-4-picoline to nevirapine without isolation of the cyclization intermediate. The optimized process operates with a total residence time of 10 min and delivers crude nevirapine in 91.9% overall isolated yield across two reaction steps, with a space-time yield of ∼365 g/h/L and 99.6 A% HPLC purity. Furthermore, we developed an on-demand continuous generation of NaHMDS in diglyme (up to ∼2.0 M) using a sodium packed-bed column reactor. Using on-demand generated NaHMDS, the telescoped synthesis yielded crude nevirapine in 90.7% isolated yield (∼340 g/h/L space-time yield and 99.5 A% purity), providing a scalable and cost-effective alternative to NaH applied in the current commercial synthesis. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acs.oprd.6c00277.s001 https://figshare.com/articles/journal_contribution/Telescoped_Two-Step_Continuous-Flow_Synthesis_of_Nevirapine_Enabled_by_the_On-Demand_Generation_of_NaHMDS/34046531 CC BY-NC 4.0