Toluene → N-(4-(3-(4-(7-(5-methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)ureido)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a 50 mL round bottom flask, 2-chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline (0.15 g, 0.00045 mol; prepared as described in Example 2; Scheme 6B), N-(4-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)phenyl)acetamide (0.23 g, 0.00059 mol; prepared according to the methods described in Scheme 9), cesium carbonate (0.44 g, 0.00135 mol), toluene (10 mL), EtOH (4 mL) and water (2 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd (PPh3)2Cl2 (0.022 g, 0.0000315 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 3 h. The reaction mixture was cooled to room temperature to get the precipitate. The precipitate was collected by filtration to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 3% MeOH in chloroform). The compound was further purified by flash column chromatography using 230-400 silica gel and 1.5% MeOH in chloroform to yield the title compound [0.0252 g, 10%]. 1H NMR (400 MHz, DMSO-d6): δ 9.86 (s, 1H), 8.92 (s, 1H), 8.67 (s, 1H), 8.42 (d, J=8.8 Hz, 2H), 8.01 (d, J=8.8 Hz, 2H), 7.74 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.39 (d, J=8.8 Hz, 2H), 7.17 (d, J=3.2 Hz, 1H), 6.32 (d, J=2.8 Hz, 1H), 3.83 (s, 4H), 3.80 (s, 4H), 2.41 (s, 3H), 2.02 (s, 3H). LC-MS (ESI): Calculated mass: 562.2; Observed mass: 563.1 (RT: 0.64 min).

Provenance & Evidence