Sodium Carbonate → HCID 178481012, compound

Participants

Reaction Steps

A mixture of trans 3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AD) (0.300 g, 0.00068 mol), 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (int AV) (0.304 g, 0.00102 mol), sodium carbonate (0.180 g, 0.00170 mol) in 1,2-dimethoxyethane (10 mL) and water (20 mL) was stirred rapidly and tetrakis(triphenylphosphine)palladium(0) (0.047 g, 0.000040 mol) added. The reaction mixture was stirred 18 hours at 80° C. The solvents were removed in vacuo and the residue was partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over magnesium sulfate, and the solvent was removed in vacuo. The product was purified by flash column chromatography on silica using dichloromethane/methanol/ammonium hydroxide (95:5:0.5). The solvent was removed in vacuo to give trans-1-[4-(4-methylpiperazino)cyclohexyl]-3-(2-phenoxy-5-pyrimidinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.155 g, 0.00032 mol): 1H NMR (DMSO-d6, 400 MHz) 8.78 (s, 2H), 8.25 (s, 1H), 7.48 (t, 2H), 7.28 (t, 1H), 7.27 (d, 2H), 4.65 (m, 1H), 1.44-2.36 (m, 20H); TLC (dichloromethane/methanol/ammonium hydroxide=90:10:0.5) Rf 0.33.

Provenance & Evidence