Sodium Carbonate → 2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-(5-bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 25 (0.5 mmol) in 1,4-dioxane (2 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.5 mmol), Na2CO3 (1.5 mmol of a 3.0 M aq. solution) and Pd(PPh3)4 (0.025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 150° C. for 10 min. The reaction mixture is diluted with water (10 mL). The aqueous layer is washed with DCM (2×50 mL) and acidified to pH 5 using aqueous HCl (1 N). The resulting mixture is extracted with DCM (2×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated to yield a crude 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 26 which is used without further purification. 1H NMR (400 MHz, d6-DMSO) δ 9.65 (s, 1H), 8.79 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.30 (s, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 3.60-3.70 (m, 2H), 3.50-3.58 (m, 2H), 3.20-3.26 (m, 2H). MS (m/z) (M+1)+: 402.1.

Provenance & Evidence