To 50% 1-propylphosphonic acid cyclic anhydride in DMF (9.9 μL, 0.017 mmol) were added additional DMF (0.5 mL), DIPEA (9.9 μL, 0.0567 mmol) and cis-4-(7-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylic acid (10.0 mg, 0.0142 mmol). The mixture was stirred at room temperature for 30 minutes. Hydroxylamine hydrochloride (2.0 mg, 0.0283 mmol) was added and the mixture was stirred at room temperature overnight. The crude mixture was purified by MDP to obtain the title compound (5.2 mg, 51% yield). 1H NMR (400 MHz, methanol-d4) d ppm 1.29 (t, J=7.1 Hz, 6H), 1.68-1.82 (m, 4H), 2.00-2.16 (m, 4H), 2.52 (br. s., 1H), 2.73 (t, J=11.1 Hz, 1H), 3.19 (s, 3H), 3.38 (d, J=21.7 Hz, 2H), 3.90 (s, 3H), 4.11 (qd, J=7.3, 7.1 Hz, 4H), 4.55 (s, 2H), 6.95-7.04 (m, 1H), 7.14 (s, 1H), 7.39 (br. s., 1H), 7.65 (d, J=8.1 Hz, 1H), 8.33 (br. s., 2H). MS (ES+): m/z 721.19 (100) [MH+]; HPLC: tR=0.97 min (UPLC, purity).
