Iodine → 1-Cyclobutyl-2-iodo-6-(pyrimidin-2-yloxy)-1h-indole-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

T6 a solution of 1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (4.24 g, 20 mmol) in THF (60.0 mL) at −78° C. was added LDA (30.7 mL, 46.0 mmol) and iodine (7.62 g, 30.0 mmol). The mixture was stirred at −78° C. for 10 min, warmed to room temperature and stirred for 3 h. The reaction mixture was poured into ice-water (500 mL) and the precipitate was filtered and washed with water and CH2Cl2. After drying in air the crude iodide obtained (3.99 g) was taken up in DMF (25 mL) and Cs2CO3 (9.78 g, 30.0 mmol) and 2-chloropyrimidine (2.18 g, 19.0 mmol) were added to this solution. The mixture was stirred at 70° C. for 30 min, poured into ice water (200 mL) and the precipitate was collected on a filter, washed with water and purified on silica gel (CH2Cl2/EtOAc, 9.75:0.25) to provide 1-cyclobutyl-2-iodo-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (1.52 g, 47%).

Provenance & Evidence