Diethyl (4-{[4-({7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate → {4-[4-(6-Bromo-2-methylcarbamoyl-pyridin-3-ylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-benzyl}-phosphonic acid diethyl ester

Participants

Reaction Steps

Prepared analogously to Compound 1B replacing Compound 10 with 3-amino-6-bromo-N-methylpyridine-2-carboxamide (Compound 6D, 279 mg, 1.21 mmol). The reaction mixture was concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0→5% MeOH in DCM] to afford 661 mg of the title compound (78%). 1H NMR (400 MHz, CD3OD) δ 8.94-9.11 (m, 1H), 8.37 (s, 1H), 7.68 (d, J=7.1 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 7.07 (t, J=2.0 Hz, 1H), 6.94 (td, J=2.4, 8.2 Hz, 1H), 4.04-4.16 (m, 4H), 3.88 (s, 3H), 3.33-3.34 (m, 1H), 3.28 (s, 1H), 2.94 (s, 3H), 1.29 (t, J=7.1 Hz, 6H). MS (ESI): m/z 647.53/649.53 [M+H]+. UPLC: tR=1.49 min (UPLC-TOF: polar—2 min).

Provenance & Evidence