Cesium carbonate → HCID 178476881, Verbindung

Beteiligte Stoffe

Reaktionsschritte

To a suspension of 7-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-4-(trans-4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 308C, 130.0 mg, 0.29 mmol), diethyl [(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate (Compound 308A, 80.9 mg, 0.29 mmol), Pd(OAc)2 (3.31 mg, 0.015 mmol), Xantphos (17.1 mg, 0.029 mmol), and Cs2CO3 (192.2 mg, 0.59 mmol) in dry dioxane (1.2 mL) was bubbled nitrogen for 2 min. This mixture was then irradiated at 160° C. for 40 min in a CEM microwave reactor. After cooled to room temperature, the reaction mixture was filtered and the filtrate was concentrated and purified by silica gel chromatography (1-5% MeOH in DCM) to give 1.9 mg of the title compound (yield: 1%). 1H NMR (CDCl3, 400 MHz): δ=1.29 (t, J=7.2 Hz, 6 H), 1.45 (m, 2 H), 1.63 (m, 2 H), 1.90 (m, 2 H), 2.16 (m, 2 H), 2.50 (m, 1 H), 3.18 (d, J=21.2 Hz, 2 H), 3.22 (s, 3 H), 3.77 (m, 1 H), 3.94 (s, 3 H), 4.04-4.10 (m, 4 H), 4.39 (s, 2 H), 7.41 (d, J=8.4 Hz, 1 H), 8.04 (s, 1 H), 8.45 (s, 1 H), 9.33 (d, J=8.0 Hz, 1 H), 10.86 (s, 1 H). MS (ES+): m/z 679.23 [MH+]. HPLC: tR=1.21 min (UPLC TOF, polar—3 min).

Herkunft & Nachweise