2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → 4-(4-Methyl-2-(2-propylthiazolo[5,4-b]pyridin-7-ylamino)phenylthio)phenol

Participants

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 (40.4 mg, 0.118 mmol), tris(dibenzylideneacetone)-dipalladium (27 mg, 0.0295 mmol), and sodium tert-butoxide (87.7 mg, 0.885 mmol). A solution of the product of Example 5G (125.5 mg, 0.590 mmol) in anhydrous toluene (5 mL) was added via syringe, followed by the product from Example 6c (136 mg, 0.590 mmol). The reaction was heated at reflux in a preheated 110° oil bath for 14 hours, cooled to room temperature, treated with additional 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (40.4 mg) and tris(dibenzylideneacetone)dipalladium (27 mg), and heated at reflux for an additional 7 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 15% to 30% ethyl acetate/methylene chloride gave impure material. Purification by silica gel flash chromatography with a gradient of 1% to 2% methanol/methylene chloride afforded the desired title compound as a light yellow solid (20 mg, 0.049 mmol, 8%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.03 (t, J=7.35 Hz, 3H) 1.76-1.94 (m, 2H) 2.31 (s, 3H) 3.10 (t, J=7.35 Hz, 2H) 5.76 (s, 1H) 6.67-6.73 (m, 2H) 6.96-7.04 (m, 1H) 7.08-7.14 (m, 1H) 7.20 (d, J=8.46 Hz, 2H) 7.29 (s, 1H) 8.14 (d, J=5.52 Hz, 1H) 8.55 (s, 1H) 9.73 (s, 1H); MS (DCI/NH3) m/z 408 (M+H)+.

Provenance & Evidence