(1-hydroxy-4-(4-isothiocyanatobenzamido)butane-1,1-diyl)diphosphonic acid (DM-22)

A solution of cathecol borane in THF 1 M (0.88 mL, 0.88 mmol) was added to compound 2 (63 mg; 0.28 mmol) under N₂ atmosphere. The reaction mixture was stirred at RT for 1 h. Then, P(OSiMe₃)₃ (347 mg, 1.16 mmol) was added to the reaction mixture and stirred at rt for 16 h. The solvent was removed in vacuo to give a crude residue, which was triturated with CHCl₃. The crude oil was dissolved in a solution of NaHCO₃ 0.4 M (2 mL) and thiophosgene (228 mg, 1.98 mmol) was added to the reaction mixture and stirred at RT for 2 h. Finally, the reaction mixture was extracted with dichloromethane (DCM). The combined organic layers were dried over MgSO₄, and filtered, and the solvent was removed in vacuo to give a residue, which was triturated with hexane to obtain the final product (20 mg, yield 24%).¹H-NMR (D₂O): δ 1.90–2.15 (m, 4 H, CH₂); 3.45 (t, 2 H, J = 6.6 Hz, CH₂); 7.43 (d, 2 H, J = 8.8 Hz, Ar), 7.80 (d, 2 H, J = 8.8 Hz, Ar) ppm.¹³C-NMR (D₂O): δ 167.70, 129.37, 128.93, 126.39, 124.06, 123.70, 76.66, 40.56, 31.24, 23.52 ppm.³¹P- NMR (D₂O) δ 19.23 ppm; ESI-MS m/z calculated for C₁₂H₁₆N₂O₈P₂S, 410.01; found, 409.45. [M - H⁺].