Phenylacetyl isothiocyanate → N-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-ylamino)phenyl carbamothioyl)-2-phenylacetamide

Participants

Reaction Steps

To a stirred solution of 418 (200 mg, 0.59 mmol) in a mixture of anhydrous toluene/ethanol (15mL/15mL) was slowly added a solution of 2-phenylacetyl isothiocyanate (522 mg, 2.95 mmol) in a mixture of anhydrous toluene/ethanol (5mL/5mL). The reaction mixture was stirred at room temperature for 4 hrs under nitrogen, concentrated, and adsorbed on silica gel. The crude material was purified by flash column chromatography (eluents 2% of NH4OH in methanol/CH2Cl2 from 5/95 to 10/90) followed by trituration with AcOEt (with traces of acetone)/hexanes, to afford title compound 415 (183 mg, 60% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.51 (s, 1H), 11.81 (s, 1H), 8.82 (bs, 1H), 8.22 (d, J=5.5 Hz, 1H), 7.91 (dd, J=12.4, 2.3 Hz, 1H), 7.79 (d, J=1.1 Hz, 1H), 7.69 (d, J=0.8 Hz, 1H), 7.53 (s, 1H), 7.44 (dd, J=8.6, 2.2 Hz, 1H), 7.40-7.24 (m, 6H), 6.42 (dd, J=5.55, 2.22 Hz, 1H), 3.83 (s, 2H), 3.71 (s, 3H). LCMS: 517.0 (M+H)+.

Provenance & Evidence