2-(tert-butylamino)-8-(2-(2,4-dimethoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-3-methylquinazolin-4(3H)-one → 2-(tert-butylamino)-3-methyl-8-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-4(3H)-quinazolinone

Participants

Reaction Steps

A solution of 2-(tert-butylamino)-8-(2-(2,4-dimethoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-3-methylquinazolin-4(3H)-one (449a) (10 mg, 0.02 mmol) in 1 mL of DCM and 0.2 mL of TFA was heated in an oil bath at 50° C. for 4 h. The reaction mixture was concentrated under reduced pressure. The brown residue was partitioned between 25 mL of EtOAc and 3 mL of 0.5 N NaOH. The EtOAc layer was separated, washed with 5 mL of brine, and concentrated. The residue was purified on a silica gel column (1-5% MeOH in DCM) to afford 2-(tert-butylamino)-3-methyl-8-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)quinazolin-4(3H)-one (449) (5 mg, 70% yield) as an off white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (1H, dd, J=7.8, 1.6 Hz), 7.70 (1H, dd, J=7.4, 1.6 Hz), 7.64 (1H, d, J=1.6 Hz), 7.60 (1H, br.), 7.10 (1H, d, J=1.6 Hz), 7.06 (1H, t, J=7.6 Hz), 5.74 (1H, s), 4.06 (2H, m), 3.46 (2H, t, J=7.1 Hz), 3.39 (3H, s), 1.45 (9H, s). m/z (ESI, +ve) 366.2 (M+H)+.

Provenance & Evidence