Methanesulfonyl chloride → HCID 89783940, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(2-hydroxyethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (462) (149 mg, 0.39 mmol) in 5 mL of DCM at 0° C. was added TEA (0.27 mL, 1.96 mmol) followed by methanesulfonyl chloride (33.4 μL, 0.43 mmol). It was stirred at 0° C. for 30 min, diluted with 30 mL of DCM, washed sequentially with 5 mL of water, 5 mL of sat NaHCO3 and 5 mL of brine. The DCM solution was dried over Na2SO4 and concentrated. The brown residue was dissolved in 1 mL of DMF and treated with sodium azide (80 mg, 1.24 mmol). The mixture was heated in an oil bath at 70° C. for 45 min. It was diluted with EtOAc (50 mL) and filtered. The filtrate was washed with 2×5 mL of water. The EtOAc solution was concentrated and purified on a silica gel column (2-8% MeOH in DCM) to give 6-(2-azidoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (463a, 97 mg, 0.24 mmol, 61% yield). m/z (ESI, +ve) 405 (M+H)+. To a solution of 6-(2-azidoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrolo-4(1H)-one (463a, 97 mg, 0.24 mmol) in 3 mL of THF and water (43.2 μl, 2.39 mmol) at RT was added trimethylphosphine (0.36 mL of 1 M in THF, 0.36 mmol). It was stirred at RT for 30 min, then diluted with 50 mL of EtOAc, and washed with 5 mL of water. The organic layer was concentrated and the residue was purified on a silica gel column (5% MeOH in DCM followed by 5% of 2 M NH3 in MeOH in DCM) to provide 6-(2-aminoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (463) (68 mg, 0.18 mmol, 75% yield) as a brown amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.81 (1H, dd, J=7.4, 1.4 Hz), 7.71 (1H, s), 7.57-7.67 (1H, m), 7.35 (1H, t, J=7.7 Hz), 6.84 (1H, s), 5.99 (1H, s), 4.57 (1H, dd, J=8.4, 4.1 Hz), 3.41 (3H, br.), 2.64-2.77 (2H, m), 2.56 (3H, s), 1.92 (1H, dd, J=13.3, 4.3 Hz), 1.57-1.65 (1H, m), 1.55 (9H, s). m/z 379.1 (ESI, +ve) (M+H)+.

Provenance & Evidence