4-Aminophenol → 4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask equipped with a magnetic stir bar was added 4-amino-phenol (0.251 g, 2.3 mmol, 1.1 eq) and DMF (3 ml). The mixture was cooled to 0° C. followed by the addition of NaH (0.13, 5.4 mmol, 2.7 eq). After 10 minutes 4-Chloro-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (0.5 g, 2.1 mmol, 1.0 eq.) was added and the reaction was allowed to warm up to room temperature. After stirring at room temperature for 1 hour the reaction mixture was diluted with ethyl acetate (50 ml) and Was washed (2×) water, (1×) NaHCO3, (2×) 5% LiCl, and (1×) brine. The organic layer was dried over sodium sulfate and the solvent removed to give 4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine as a yellow solid (570 mg, 87%). 1H NMR (400 MHz, CDCl3): 8.56(s, 1H), 7.75 (s, 1H), 6.97 (d, 2H), 6.64 (d, 2H), 5.96 (dd, 1H), 5.21 (s, 2H), 3.96 (d, 1H), 3.72 (m, 1H), 2.42 (m, 1H), 2.01 (m, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 1.57 (m, 2H); MS (ESI) for C16H17N5O2: 312 (MH+).

Provenance & Evidence