Potassium Phosphate, Tribasic → rac-2-(tert-butylamino)-8-(6-(methoxymethyl)-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-methylquinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

A microwave tube was charged with 2-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-one (701; 316 mg, 0.89 mmol), 6-(methoxymethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (485b, 323 mg, 1.11 mmol), X-Phos precatalyst II (Sigma-Aldrich; 35 mg, 0.044 mmol) and K3PO4 (563 mg, 2.65 mmol). The tube was sealed and purged with argon for 5 minutes. 1,4-dioxane (2.6 mL) and water (0.65 mL) were added and Ar (g) was bubbled through the mixture for 5 min. The tube was heated at 45° C. in an oil bath for 90 min. The reaction mixture was cooled to RT and EtOAc and water were added. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-10% MeOH in CH2Cl2), to provide rac-2-(tert-butylamino)-8-(6-(methoxymethyl)-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)-3-methylquinazolin-4(3H)-one (485) (160 mg, 0.41 mmol, 46% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ ppm 12.19 (br. s., 1H), 8.07 (dd, J=7.82, 1.76 Hz, 1H), 8.00 (dd, J=7.63, 1.76 Hz, 1H), 7.22 (t, J=7.73 Hz, 1H), 6.83 (d, J=1.57 Hz, 1H), 5.85 (s, 1H), 4.65-4.72 (m, 1H), 4.61 (s, 1H), 3.65 (dd, J=9.00, 5.48 Hz, 1H), 3.55 (s, 3H), 3.46 (t, J=8.61 Hz, 1H), 3.41 (s, 3H), 1.65 (s, 9H). m/z (ES, +ve) 396.0 (M+H)+.

Provenance & Evidence