Potassium Phosphate, Tribasic → HCID 89783447, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 8-bromo-2-(tert-butylamino)-3-(tetrahydro-2H-pyran-4-yl)quinazolin-4(3H)-one (515d, 70 mg, 0.184 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, 93 mg, 0.276 mmol), X-Phos precatalyst II (7.24 mg, 9.20 μmol), and potassium phosphate (117 mg, 0.552 mmol) in 1,4-dioxane (1.5 mL)/water (0.4 mL) was sparged with nitrogen for 3 min at RT; the reaction mixture was stirred at 40° C. for 1.5 h. The reaction mixture was diluted with EtOAc (100 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (3×75 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was loaded onto the column and was purified via automated flash chromatography (silica gel) with 0-6% 2 M ammonia in MeOH/DCM to give (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)quinazolin-4(3H)-one (515, 10 mg, 0.023 mmol, 12% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (d, J=6.65 Hz, 3H) 1.65 (s, 9H) 1.85 (d, J=11.15 Hz, 2H) 2.33-2.48 (m, 2H) 3.61 (t, J=11.54 Hz, 2H) 4.17 (dd, J=11.74, 4.50 Hz, 2H) 4.65 (q, J=6.72 Hz, 1H) 4.88 (s, 1H) 5.59-5.68 (m, 1H) 5.70 (s, 1H) 6.82 (d, J=1.17 Hz, 1H) 7.21 (t, J=7.73 Hz, 1H) 8.00 (dd, J=7.73, 1.47 Hz, 1H) 8.04 (dd, J=7.83, 1.37 Hz, 1H) 12.27 (br. s., 1H). MS (ESI, pos. ion) m/z: 436.1 (M+1).

Provenance & Evidence