7-Amino-2-methyl-2,3-dihydro-1H-isoindol-1-one → Bis(2,2,2-trifluoroethyl) [3-methoxy-4-({4-[(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino) benzyl]phosphonate

Participants

Reaction Steps

The title compound was prepared according to the procedure for Example 102 using bis(2,2,2-trifluoroethyl) (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 124A, 67.0 mg, 0.119 mmol) and 7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one (Preparation XXXVIII, 26.9 mg, 0.166 mmol). The crude product was adsorbed onto a pre-filled solid loading cartridge and purified using the Teledyne/ISCO Combiflash system eluting with 0-5% MeOH:CH2Cl2. The desired fractions were pooled together and concentrated in vacuo. The material was further purified by MDP (under basic conditions; ammonium bicarbonate buffer, pH 9), which afforded the title material as an off-white solid, 54.8 mg (64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.60 (s, 1H), 9.13 (s, 1H), 8.40 (s, 1H), 8.37 (br s, 1H), 7.49 (br d, J=7.1 Hz, 1H), 7.37 (br t, J=7.1 Hz, 1H), 7.15 (d, J=7.6 Hz, 1H), 7.06 (s, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.60-4.74 (m, 4H), 4.45 (s, 2H), 3.74 (s, 3H), 3.61 (d, J=22.2 Hz, 2H), 3.06 (s, 3H). MS (ES+): m/z 688.08 (100) [MH+]. HPLC: tR=3.72 min (ZQ3, polar—5 min).

Provenance & Evidence