Dichloromethane → Diethyl (4-{[4-({7-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

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Reaction Steps

A mixture of diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (10.0 mg, 0.0159 mmol), 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.02 mg, 0.0318 mmol), potassium carbonate (6.60 mg, 0.0477 mmol), 1,4-dioxane (0.4 mL), H2O (0.1 mL) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.30 mg, 0.00159 mmol) was evacuated and purged with N2. The mixture was irradiated in a microwave reactor at 100° C. for 30 minutes. The crude mixture was passed through a Thiol-SPE column to remove Pd and purified by MDP to obtain the title compound (2.1 mg, 19.6% yield). 1H NMR (400 MHz, CD3OD) δ=1.25 (t, J=7.1 Hz, 6 H), 3.21 (s, 3 H), 3.30 (d, J=22.7 Hz), 3.35 (s, 3 H), 3.79 (t, J=5.2 Hz, 2 H), 4.01-4.13 (m, 4 H), 4.37 (t, J=5.2 Hz, 2 H), 4.60 (s, 2 H), 7.37 (dd, J=8.6, 2.3 Hz, 2 H), 7.57 (d, J=8.6 Hz, 2 H), 7.72 (d, J=8.8 Hz, 1 H), 7.94 (s, 1 H), 8.08 (s, 1 H), 8.36 (s, 1 H), 8.68 (br. s., 1 H). MS (ES+): m/z 674.34 (100) [MH+]; HPLC: tR=1.05 min (UPLC, purity).

Provenance & Evidence