Sodium Carbonate → 1-(2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of sodium 1-(2-(4-(5-bromopyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylate 13 (0.05 mmol) in 1,4-dioxane (1.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.05 mmol), 3M Na2CO3 (0.15 mmol) and Pd(PPh3)4 (0.0025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 150° C. for 10 min. Purification by prep-HPLC (ACN gradient 10-70%) affords 1-(2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid A3. 1H NMR (400 MHz, d6-DMSO) δ 9.68 (s, 1H), 8.78 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.71 (d, J=9.2 Hz, 2H), 7.28 (t, J=74.0 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H), 6.98 (d, J=8.8 Hz, 1H), 4.28 (t, J=4.8 Hz, 2H), 3.51 (m, 2H), 3.23 (m, 4H), 1.24 (t, J=7.2, 6H). MS (m/z) (M+1)+: 485.2.

Provenance & Evidence