2,6-Lutidine → HCID 131730094, compound

Participants

Reaction Steps

Compound 56.2 (338 mg, 0.57 mmol) in CH3CN (6.0 mL) was treated with 2,6-lutidine (662 μL, 5.7 mmol) and TMSBr (368 μL, 2.9 mmol) at 0° C. for 30 min. The mixture was warmed to r.t. and stirred for 30 min. The mixture was cooled to −40° C. and treated with triethylamine (794 μL, 5.7 mmol) in MeOH (2 mL). The mixture was warmed to r.t. and concentrated in vacuo. The residue in DMF (2.0 mL) was treated with ammonium fluoride (1.06 g, 28.5 mmol) and heated to 80° C. for 5 h. The solvent was removed in vacuo and residue was subjected to reverse phase HPLC eluting with 5-50% CH3CN-water gradient to give 56.3 (76 mg, 30% yield, 2 steps): white solid; 1H NMR (CD3OD, 300 MHz) 8.71 (s, 1H), 8.49 (s, 1H), 6.75 (d, J=8.1 Hz, 2H), 7.61 (app t, J=6.6 Hz, 1H), 7.52 (m, 2H), 6.71 (m, 2H), 6.15 (t, J=18.3 Hz, 1H), 5.17 (d, J=52.5 Hz, 1H), 4.50 (m, 2H); 31P NMR (D2O 121.4 MHz) 12.2; 19F NMR (D2O, 282 MHz) −200 (m, 1F); MS (ESI) m/z 451 [M+H]+.

Provenance & Evidence