4-(5-Chloro-2,3-dihydro-indol-1-yl)-6,7-dimethoxy-quinazoline → 7-Hydroxy-6-methoxyquinazoline

Participants

Reaction Conditions

Reaction Steps

4-(5-Chloro-2,3-dihydro-indol-1-yl)-6,7-dimethoxy-quinazoline (1.00 g, 2.93 mmol; from Example 3) was added to molten pyridinium hydrochloride (10.14 g, 88 mmol) at 170° C. The mixture was stirred at 170° C. for 0.5-1.0 hours (until <5% starting material remained by anal. RP-HPLC), and then poured into ice/water (110 mL). The precipitated orange solid was recovered by filtration, dried by azeotropic removal of H2O with CH3CN at 40° C. in vacuo, dissolved in 15% i-PrOH/CHCl3 (75 mL) and washed with saturated aqueous NaHCO3 (2×). The organic phase was dried over Na2SO4(s), filtered and concentrated in vacuo. The residue (~800 mg) was triturated with CHCl3 (60 mL) and filtered to recover the 6,7-diol (typically 200 mg, 94% purity; used without further purification)(M.P. 200° C. (dec); LC-MS: 314 (MH+); anal. RP18-HPLC RT: 4.07 min.). The filtrate was flash chromatographed on silica (40 to 80% acetone/CH2Cl2) to afford ~550 mg of the pure 6-methoxy-quinazolin-7-ol product (M.P. 175° C. (dec); LC-MS: 328 (MH+); anal. RP18-HPLC RT: 4.07 min.).

Provenance & Evidence