Water → HCID 89783660, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (1S,3R)—N1-(8-bromo-3-methylquinoxalin-2-yl)cyclohexane-1,3-diamine (483b, 1.62 g, 4.83 mmol), (R)-6-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (705, 2.53 g, 9.65 mmol), dichlorobis(p-dimethylaminophenylditbutylphosphine)palladium (II) (0.171 g, 0.24 mmol), and potassium phosphate (3.07 g, 14.48 mmol) in 1,4-dioxane (38.6 mL)/water (9.65 mL) was sparged with nitrogen for 3 min and was stirred at 80° C. for 45 min. The reaction mixture was diluted with water (200 mL), added to a separatory funnel, and extracted with 3:2 chloroform/IPA (5×100 mL); the combined organic layers were separated, dried over Na2SO4, and concentrated. The crude product in 10% MeOH/DCM was loaded onto the column and was purified via automated flash chromatography (silica gel) with 100% DCM to 50% 2 M ammonia in MeOH/DCM to give (R)-2-(3-4(1S,3R)-3-aminocyclohexyl)amino)-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (483, 1.59 g, 4.07 mmol, 84% yield) as a brown amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.16 (m, 1H) 1.29-1.42 (m, 3H) 1.43 (d, J=6.65 Hz, 3H) 1.82 (d, J=11.15 Hz, 2H) 1.99-2.18 (m, 3H) 2.55 (s, 3H) 2.82 (t, J=10.27 Hz, 1H) 3.33 (br. s., 1H) 4.04-4.14 (m, 1H) 4.56 (q, J=6.52 Hz, 1H) 7.03 (s, 1H) 7.13 (br. s., 1H) 7.34 (t, J=7.82 Hz, 1H) 7.60 (dd, J=7.92, 1.08 Hz, 1H) 7.64 (s, 1H) 7.86-7.91 (m, 1H) 12.08 (br. s., 1H). MS (ESI, pos. ion) m/z: 391.1 (M+1).

Provenance & Evidence