Butane → 4-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde

Participants

Reaction Steps

To a solution of toluene (100 mL) in a 500 mL round-bottom flask equipped with a reflux condenser was added 1,4-bis(diphenyl)phosphino)-butane (4.25 mg, 0.997 mmol) and bis(benzonitrile)dichloro-palladium (385 g, 0.997 mmol). Nitrogen was bubbled through the reaction mixture for 1 minute and the resulting suspension was stirred at room temperature for 30 minutes. THF (125 mL) and EtOH (50 mL) were then added. To the resulting mixture was added (1-benzenesulfonyl-1H-indol-5-yl)-(6-iodo-quinazolin-4-yl)-amine 20 (3.5 g, 6.6 mmol), 4-formylphenylboronic acid (1.99 g, 13.3 mmol) and 2M aq Na2CO3 (6.7 mL). The mixture was heated at reflux under an atmosphere of N2 for 15 hours. The solvent was removed under reduced pressure and the residue was purified using flash chromatography (silica gel, EtOAc/hexanes 1:1) to provide 3.1 g of 4-[4-(1-benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde 22 in 92% yield. 1H NMR (DMSO-d6; 400 MHz): δ: 9.24 (s, 1H, NH), 8.84 (s, 1H), 8.33 (dd, 1H, J=8.9 Hz and 1.7 Hz), 8.01 (m, 4H), 7.90 (m, 2H), 7.70 (m, 2H), 7.60 (m, 3H), 6.92 (dd, 1H, J=3.7 Hz and 0.6 Hz); MS (Cl) m/e 505.1 (M++1, 100).

Provenance & Evidence