Trifluoroacetic acid → HCID 71732053, compound

Participants

Reaction Steps

A solution of the above obtained 0.53 g of 1:1 mixture of tert-butyl (1-hydroxy-2-methylpropan-2-yl)carbamate and tert-butyl (1-(2-methoxyethoxy)-2-methylpropan-2-yl)carbamate in 10 mL of DCM and TFA (1.4 mL, 19.60 mmol) was stirred at RT for 2 h. It was concentrated under reduced pressure. The residue was treated with 10 mL of 1 N NaOH, and extracted with 3×30 mL of EtOAc. The combined organic layers were washed with 5 mL of brine, dried over Na2SO4 and concentrated to give an off-white amorphous solid containing a 1:1 mixture of tert-butyl (1-(2-methoxyethoxy)-2-methylpropan-2-yl)carbamate (317b) [m/z (ESI, +ve) 148.0 (M+H)+] and 2-amino-2-methylpropan-1-ol [m/z (ESI, +ve) 90.0 (M+H)+]. This material was used without further purification. A solution of the above obtained off-white amorphous solid containing a 1:1 mixture of tert-butyl (1-(2-methoxyethoxy)-2-methylpropan-2-yl)carbamate (317b) [m/z (ESI, +ve) 148.0 (M+H)+] and 2-amino-2-methylpropan-1-ol [m/z (ESI, +ve) 90.0 (M+H)+], and 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (126) (135 mg, 0.45 mmol), and TEA (0.13 mL, 0.91 mmol) in 1.5 mL of DMSO in a sealed glass tube was heated in a microwave at 150° C. for 0.5 h. The reaction mixture was diluted with 75 mL of EtOAc, washed with 5 mL of water followed by 5 mL of brine. The organic layer was dried over Na2SO4 and concentrated. The residue was purified on a silica gel column (1-5% MeOH in DCM) to give 2-(3-((1-(2-methoxyethoxy)-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (40 mg, 20% yield) in 92% pure as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.87 (1H, br.), 7.82 (1H, d, J=7.6 Hz), 7.61 (1H, d, J=8.0 Hz), 7.36 (1H, t, J=7.7 Hz), 7.00 (2H, m), 5.92 (1H, br.), 3.71 (2H, s), 3.59 (2H, m), 3.44 (2H, m), 3.20 (3H, s), 3.18 (2H, m), 2.87 (2H, m), 2.55 (3H, s.), 1.54 (6H, s). m/z (ESI, +ve) 424.0 (M+H)+.

Provenance & Evidence