3-[(2,6-dimethylphenoxy)methyl]-4-methoxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(chloromethyl)-4-methoxybenzaldehyde (300 mg, 1.625 mmol, 1.0 equivalent) and 2,6-dimethylphenol (218 mg, 1.787 mmol, 1.1 equivalent) in 10 ml acetonitrile was added potassium carbonate (1.1 g, 8.12 mmol, 5.0 equivalents). The mixture was heated to 150 C in a microwave for 30 min. Upon completion, the mixture was filtered and dried down to give 3-[(2,6-dimethylphenoxy)methyl]-4-methoxybenzaldehyde (400 mg, 91% yield) as a yellow solid. A portion of which (100 mg, 0.370 mmol, 1.0 equivalent) was taken up in ethanol (4 ml), and to it was added 2-amino-N-(pyridin-3-ylmethyl)benzamide (92 mg, 0.407 mmol, 1.1 equivalent) followed by ytterbium(III) trifluoromethanesulfonate (45.9 mg, 0.074 mmol, 0.2 equivalent). The mixture was heated to 80 C for 2 h. Upon completion, the mixture was dried down and chromatographed on silica gel with 0-30% EtOAc (ethyl acetate)/hexanes gradient elution to give the desired 2-{3-[(2,6-dimethylphenoxy)methyl]-4-methoxyphenyl}-3-(pyridin-3-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one (110 mg, 62.0% yield) as a tan solid. 1H nuclear magnetic resonance (400 MHz, DMSO-d6) δ ppm 8.39-8.45 (m, 2 H), 7.60-7.67 (m, 2 H), 7.48 (d, J=2.35 Hz, 1 H), 7.15-7.35 (m, 4 H), 6.94-7.02 (m, 3 H), 6.84-6.93 (m, 1 H), 6.60-6.69 (m, 2 H), 5.82 (d, J=2.35 Hz, 1 H), 5.07 (d, J=15.65 Hz, 1 H), 4.64 (d, J=2.74 Hz, 2 H), 3.99 (d, J=15.45 Hz, 1 H), 3.73 (s, 3 H), 2.12 (s, 6 H); liquid chromatography mass spectrometry: (electrospray+ve), m/z 480.2 (MH)+ (mass of molecular weight plus 1); HPLC: tR=5.05 min, UV254=100%. High-resolution mass spectroscopy (electrospray ionization): m/z calculated for C30H30N3O3 [M+H]+480.2282, found 480.2291. The mixture was heated to 150 C in a microwave for 30 min Upon completion, the mixture was filtered dried down