Potassium Phosphate, Tribasic → (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-(3-(methylsulfonyl)propyl)quinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 2-(tert-butylamino)-8-iodo-3-(3-(methylsulfonyl)propyl)quinazolin-4(3H)-one (105 mg, 0.227 mmol) and (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) (89 mg, 0.272 mmol) in 1,4-dioxane (1.0 mL)/water (0.2 mL) followed by potassium phosphate (0.056 mL, 0.680 mmol) and XPhos precatalyst II (8.92 mg, 0.011 mmol, Sigma Aldrich, St. Louis, Mo.). The reaction mixture was stirred and heated in an oil bath at 45° C. for 2 h, then another 0.3 equiv. of boronic ester 705 was added and the reaction was stirred at RT overnight. More boronic ester 705 (0.3 equiv) was added and the reaction was stirred at 45° C. for 1 h. The mixture was cooled to RT and diluted with water (15 mL). The suspension was filtered and the solid was purified with silica gel chromatography (eluted with 1-4% MeOH in DCM) to give (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-(3-(methylsulfonyl)propyl)quinazolin-4(3H)-one (85 mg, 0.180 mmol, 80% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 472 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.83 (1H, s), 7.83-7.93 (2H, m), 7.60 (1H, s), 7.19 (1H, t, J=7.6 Hz), 6.68 (1H, d, J=1.4 Hz), 5.95 (1H, s), 4.52 (1H, q, J=6.6 Hz), 4.28 (2H, t, J=7.2 Hz), 3.21 (2H, t, J=7.5 Hz), 3.02 (3H, s), 2.00-2.10 (2H, m), 1.50 (9H, s), 1.36 (3H, d, J=6.7 Hz).

Provenance & Evidence