Trimethylsilyl iodide → HCID 72700425, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of ethyl hydrogen diethoxyphosphoryl((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)phosphoramidate (9) (0.040 g, 0.056 mmol) in DCM (5 mL) was added iodotrimethylsilane (0.067 g, 0.34 mmol) dropwise, under a nitrogen atmosphere at 0° C. The mixture was stirred for 2 h at 0° C. and the solvent was removed under reduced pressure. The residue was cooled to 0° C. and treated with a mixture of acetone (10 mL) and H2O (0.20 mL). After stirring at 0° C. for 1 h, the mixture was stirred at room temperature overnight. The resulting suspension was filtered and the solid was washed with acetone (20 mL), dried and purified by preparative HPLC to afford ((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)(phosphono)phosphoramidic acid (10) (0.025 g, 0.040 mmol, 71% yield) as a white solid. Preparative HPLC Conditions: Column: KROMASIL® C-4 (250×21.2) mm, 5 μm, Mobile Phase A: 10 mM ammonium acetate in water, Mobile Phase B: acetonitrile, Gradient: 20 to 40% B over 7 min, 100% B for 12.5 min., Flow Rate: 17 mL/min., Retention time: 9 min.; 1H NMR (400 MHz, DMSO-d6) δ (ppm) 4.78 (d, J=3.76 Hz, 2H), 6.96 (br. s., 1H), 7.23 (dd, J=6.53, 5.27 Hz, 1H), 7.31 (dd, J=7.03, 1.25 Hz, 1H), 7.41 (d, J=7.78 Hz, 1H), 7.51-7.61 (m, 5H), 7.73 (td, J=7.65, 1.76 Hz, 1H), 7.80-7.88 (m, 1H), 7.96 (dd, J=8.41, 1.13 Hz, 1H), 8.23 (d, J=4.27 Hz, 1H), 9.11 (d, J=2.01 Hz, 1H) 9.17 (t, J=2.01 Hz, 1H), 9.67 (d, J=2.01 Hz, 1H); 31P (162.0 MHz, DMSO-d6) δ (ppm) −8.820, −8.917, −15.535, −15.629; LCMS Method I: retention time 1.56 min, [M−1]=627. HPLC Method H: Purity 95.0%, retention time 5.27 min.

Provenance & Evidence