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. 2021 Aug 9;64(16):12245–12260. doi: 10.1021/acs.jmedchem.1c00887

Scheme 1. Synthesis of Bisphosphonate Vinyl Sulfone (BP-VS) Derivatives (7 and 11).

Scheme 1

Reagents and conditions: (a) paraformaldehyde, MeOH, reflux, 6 days, then p-TsOH, toluene, reflux, 40 h, yield = 74% for the two steps; (b) CH2Cl2/pyridine, acetic anhydride, rt, 16 h, yield = 46%; (c) CH2Cl2/2-propanol, Et3N, rt, 16 h, yield = 78%; (d) HCl(aq) (6 M), reflux, 16 h, yield = quanti. for 6 and 10; (e) divinyl sulfone, Na2CO3, H2O, rt, yield = 96% for 7 and quantitative for 11; (f) HCHO, diisopropyl phosphite, THF, reflux, 16 h, yield = 57%.