Thionyl Chloride → HCID 21084065, compound

Participants

Reaction Steps

To a suspension of the compound of Example 88 (130 mg, 0.32 mmol) in THF (2 mL) was added NaH (14 mg of 60% dispersion in oil, 0.35 mmol). DMF (0.5 mL) was added to aid solubility and the reaction was stirred for 1 h. Thionyl chloride (25 μL, 0.35 mmol) was added to the reaction mixture cooled in an ice-bath. The mixture was stirred in the ice-bath for 30 mins before quenching the reaction with water (20 mL) and basifying with NaHCO3(aq). The product was extracted into DCM (2×15 mL) and the combined DCM layers dried over MgSO4, filtered and concentrated in vacuo to give ethyl 7-(4-chloromethylphenyl)-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-b]pyridine-2-carboxylate LCMS (ES+) RT 3.97 minutes, 424 (M+H)+. To a solution of this compound in DMF (1 mL) was added 2-methylimidazole (13 mg, 0.16 mmol) and caesium carbonate (52 mg, 0.16 mmol) and the mixture heated at 80° for 3 h. DMF was removed in vacuo and the residue purified by column chromatography (silica, 40–100% EtOAc in isohexane followed by 5% MeOH in DCM) and also mass directed hpic to give the title compound as a solid (3 mg). δH (MeOH-d4) 7.47–7.27 (10 H, m), 7.06 (1H, d, J 1.4 Hz), 6.82 (1H, d, J 1.4 Hz), 6.50 (1H, d, J 9.6 Hz), 5.26 (2H, s), 4.00 (2H, q, J 7.1 Hz), 2.28 (3H, s), 0.99 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.53 minutes, 470 (M+H)+.

Provenance & Evidence