Potassium Carbonate → 2-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine

Participants

Reaction Conditions

Reaction Steps

N-Benzyl-2-chloro-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (0.200 g, 0.597 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (0.263 g, 1.20 mmol, commercial) were dissolved in dioxane (10 mL) and water (2 mL). To the above solution was added K2CO3 (0.248 g, 1.79 mmol) and the reaction mixture was degassed with nitrogen for 15 minutes then PdCl2(dppf)-CH2Cl2 (0.0490 g, 0.0600 mmol) was added. The resulting reaction mixture was degassed for 20 minutes and heated to reflux at 110° C. for 14 h. The reaction mixture was allowed to cool, concentrated under reduced pressure and diluted with CH2Cl2 (10 mL). The resulting solid was filtered through a CELITE® bed and the filtrate dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-62 as described in general methods) to afford 2-(5-aminopyridin-3-yl)-N-benzyl-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (20.0 mg, 8.53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.81 (d, J=6.0 Hz, 2H), 5.46 (s, 2H), 6.54 (t, J=6.0 Hz, 1H), 6.78 (d, J=2.8 Hz, 1H), 7.26-7.54 (m, 10H), 7.75 (dd, J=2.0 Hz, J=2.8 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 8.01 (d, J=2.8 Hz, 1H), 8.58 (d, J=1.6 Hz, 1H). LCMS Condition B-47: retention time 2.20 min, [M+1]=393.2. HPLC Condition B-63: retention time 24.18 min, Purity 97.00%.

Provenance & Evidence