Sodium Carbonate → (R)-3-(4-(3-(4-cyclopropylpyrimidin-2-ylamino)-5-methylphenyl)-1H-pyrazol-1-yl)-2-hydroxypropanoic acid

Participants

Reaction Conditions

Reaction Steps

Cesium carbonate (65.2 mg, 0.20 mmol) was added along with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (19.40 mg, 0.100 mmol) dissolved in DMF (1000 μL) and (R)-methylglycidate (10 μL, 0.11 mmol) was added to vial. The reaction was warmed to 80° C. and stirred overnight. PdCl2(dppf)-CH2Cl2 (8.17 mg, 10.00 μmol) was added directly to the reaction mixture along with N-(3-bromo-5-methylphenyl)-4-cyclopropyl-pyrimidin-2-amine (30 mg, 0.1 mmol) and sodium carbonate (2M in water, 100 μL, 0.200 mmol). The mixture was stirred at 90° C. overnight and then stirred at 100° C. for 72 hours. Si-Dimercaptotriazole (Si-DMT) (222 mg, 0.126 mmol) was added as a means of scavenging the palladium and the vial was resealed and allowed to stir for 6 hours at room temperature. The reaction mixture was filtered through an activated CELITE cartridge (HM-N) and washed with DMSO (2×1 mL). The solution was purified by reverse phase HPLC (ACN/water with ammonium hydroxide buffer) to afford (R)-3-(4-(3-(4-cyclopropylpyrimidin-2-ylamino)-5-methylphenyl)-1H-pyrazol-1-yl)-2-hydroxypropanoic acid as the ammonium salt. MS ESI calcd. for C20H22N5O3 [M+H]+ 380. found 380. 1H NMR (600 MHz, DMSO-d6) δ 9.26 (s, 1H), 8.22 (d, J=5.0, 1H), 7.92 (s, 1H), 7.79 (s, 1H), 7.68 (s, 1H), 7.30 (s, 1H), 6.91 (s, 1H), 6.75 (d, J=5.0, 1H), 4.37 (dd, J=2.7, 13.6, 1H), 3.95 (dd, J=8.7, 13.6, 1H), 3.89 (d, J=7.4, 1H), 2.24 (s, 3H), 2.03-1.94 (m, 1H), 1.09-0.98 (m, 5H).

Provenance & Evidence