HCID 71730635, compound → HCID 71730636, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (349) (61 mg, 0.14 mmol), dimethylzinc in hexanes (0.39 mL of 10% wt. in hexanes, 0.570 mmol, Strem Chemicals, Inc.,), and (A-Phos)2PdCl2 (10 mg, 0.014 mmol) in dioxane (1.42 mL) was stirred at 80° C. for 2 h when product was observed via lcms. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (2×75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 1-4% of 2 M NH3 in MeOH/DCM to give impure 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one contaminated with starting material. The impure product was purified via SFC [IC (3×15 cm, 5 μm), 60% 0.2% DEA in MeOH: EtOH: isopropanol (1:1:1) (NH4OH)/CO2, 100 bar; 65 mL/min, 220 nm; inj vol.: 1.5 mL, 3.5 mg/mL in MeOH] to give 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (350, 10 mg, 0.028 mmol, 19% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.60 (s, 9H) 2.55 (s, 3H) 2.69 (s, 3H) 2.95 (t, J=6.85 Hz, 2H) 3.61 (td, J=6.85, 2.54 Hz, 2H) 4.79 (s, 1H) 5.18 (br. s., 1H) 7.42 (t, J=7.92 Hz, 1H) 7.68 (dd, J=8.12, 1.27 Hz, 1H) 7.85 (dd, J=7.53, 1.08 Hz, 1H) 11.62 (br. s., 1H). MS (ESI, pos. ion) m/z: 364.2 (M+1).

Provenance & Evidence