Tert-Butylamine → 2-(tert-butylamino)-8-iodo-3-(2-methoxyethyl)quinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-iodo-3-(2-methoxyethyl)-2-(methylthio)quinazolin-4(3H)-one (715a; 1.33 g, 3.54 mmol) in 100 mL of DCM at 0° C. was added 3-chloroperoxybenzoic acid (77% max., 1.47 g, 6.56 mmol) and the resulting mixture was stirred for 1 h at 0° C. It was diluted with 50 mL of DCM, washed with 2×15 mL of sat NaHCO3. The DCM layer was dried over Na2SO4 and concentrated to give a yellow solid as a mixture (715b) of 8-iodo-3-(2-methoxyethyl)-2-(methylsulfonyl)quinazolin-4(3H)-one and 8-iodo-3-(2-methoxyethyl)-2-(methylsulfinyl)quinazolin-4(3H)-one. To the crude mixture (715b) in a sealable glass vessel was added tert-butylamine (3.72 mL, 35.4 mmol) and 5 mL of DMSO. The glass vessel was sealed and heated in an oil bath at 80° C. for 3 h. It was treated with 10 mL of 0.5 N NaOH, and extracted with 2×35 mL of EtOAc. The organic extracts were dried over Na2SO4 and concentrated. The residue was stirred in 25 mL of ether. The insoluble solid was filtered and rinsed with 2×10 mL of ether. The filtrate was concentrated and the residue was purified on a silica gel column (30-80% EtOAc in hexanes) to afford 2-(tert-butylamino)-8-iodo-3-(2-methoxyethyl)quinazolin-4(3H)-one (715) (0.99 g, 2.467 mmol, 70% yield for 2 steps) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.16 (1H, dd, J=7.5, 1.5 Hz), 7.94 (1H, dd, J=7.8, 1.4 Hz), 6.92 (1H, t, J=7.7 Hz), 6.46 (1H, s), 4.23 (2H, t, J=4.8 Hz), 3.66 (2H, t, J=4.7 Hz), 3.35 (3H, s), 1.58 (9H, s). m/z (ESI, +ve) 401.9 (M+H)+.

Provenance & Evidence