Aniline → N-(4-(4-methyl-2-(2-propylthiazolo[5,4-b]pyridin-7-ylamino)phenylthio)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

A dry nitrogen-purged flask was charged with 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (38.6 mg, 0.1128 mmol), tris(dibenzylideneacetone)-dipalladium (25.8 mg, 0.0282 mmol), and sodium tert-butoxide (83.8 mg, 0.8463 mmol). A solution of the product of Example 5G (120 mg, 0.5642 mmol) in anhydrous toluene (5 mL) was added via syringe, followed by the product from Example 7b (130 mg, 0.4773 mmol). The reaction was heated in a preheated 100° C. oil bath for 2.5 hours, cooled to room temperature, treated with additional 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (38.6 mg), tris(dibenzylideneacetone)dipalladium (25.8 mg) and starting aniline (130 mg), and heated at 100° C. for an additional 18 hours. The reaction was cooled to room temperature and the solvent removed by rotary evaporation in vacuo. Purification by silica gel flash chromatography with a gradient of 40% to 60% ethyl acetate/methylene chloride gave the desired title compound as a tan foam (26 mg, 10%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.01 (t, J=7.35 Hz, 3H) 1.73-1.91 (m, 2H) 2.01 (s, 3H) 2.34 (s, 3H) 3.07 (t, J=7.54 Hz, 2H) 6.78 (d, J=5.52 Hz, 1H) 6.97-7.09 (m, 1H) 7.16-7.30 (m, 3H) 7.36 (s, 1H) 7.51 (d, J=8.82 Hz, 2H) 8.15 (d, J=5.52 Hz, 1H) 8.53 (s, 1H) 9.99 (s, 1H); MS (DCI/NH3) m/z 449 (M+H)+.

Provenance & Evidence