Diisopropylethylamine → N-{3-[7-(3-dimethylamino-phenylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide

Participants

Reaction Steps

To a solution of 3-(5-amino-2-methyl-phenyl)-7-(3-dimethylamino-phenylamino)-1-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (52 mg, 0.13 mmol), 3-(4-methyl-imidazol-1-yl)-5-trifluoromethylbenzoic acid (42 mg, 0.15 mmol), and DIEA (78 μL, 0.45 mmol) in DMF is added HATU (59 mg, 0.15 mmol), and the mixture is stirred for 1 hour at room temperature. The reaction mixture is diluted with EtOAc and washed with 5% aqueous Na2S2O3 solution, saturated aqueous NaHCO3 solution, and brine. The organic layer is dried over MgSO4 and concentrated in reduced pressure. The residue is purified by recrystallization from methanol to give N-{3-[7-(3-dimethylamino-phenylamino)-1-methyl-2-oxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide (25 mg, 30%) as a yellowish solid; 1H NMR 400 MHz (DMSO-d6) δ 9.34 (s, 1H), 8.43 (s, 1H), 8.38 (s, 1H), 8.23 (s, 1H), 8.16 (s, 1H), 8.13 (s, 1H), 7.74 (s, 1H), 7.69 (s, 1H), 7.65 (d, 1H), 7.34-7.30 (m, 2H), 7.08-7.03 (m, 2H), 6.33 (d, 1H), 4.68 (d, 1H), 4.51 (d, 1H), 3.35 (s, 3H), 2.88 (s, 6H), 2.17 (s, 3H), 2.14 (s, 3H); MS m/z 656.3 (M+1).

Provenance & Evidence