1H-indole-6-carbonitrile → HCID 69200222, compound

Participants

Reaction Steps

Part A. 3-bromo-4-(6-cyano-1-ethyl-1H-indol-3-ylmethyl)-benzoic acid tert-butyl ester: A mixture of the compound of Example 10, Part A (5 g, 0.175 mol) and 6-cyanoindole (1.7 g, 0.0.12 mol) in t-butanol (60 ml) and THF (˜5 mL) was treated with potassium t-butoxide (0.012 mol) and the mixture was stirred at rt under N2. After 18 h the reaction mixture was diluted with EtOAc and washed with water and brine, dried over anh. Na2SO4, filtered and solvent evaporated. The residue was purified by flash chromatography on silica gel to provide 3-Bromo-4-[(6-cyano-1H-indol-3-yl)-hydroxy-methyl]-benzoic acid tert-butyl ester (4.05 g, 79%) as an off-white foam. 1H NMR (400 MHz, CDCl3) δ ppm 1.58 (s, 9H) 2.43 (d, J=0.39 Hz, 1H) 6.47 (d, J=0.39 Hz, 1H) 7.11 (d, J=2.20 Hz, 1H) 7.36 (d, J=8.35 Hz, 1H) 7.70 (s, 1H) 7.78 (dd, J=15.60, 8.13 Hz, 2H) 7.98 (m, 1H) 8.14 (s, 1H) 8.39 (s, 1H). This material was dissolved in methylene chloride (55 ml) and cooled in an ice/salt water bath under N2. To the cold, stirred solution was added triethylsilane (3.03 mL, 2 eq) followed by slow addition of trifluoroacetic acid (0.72 mL, 1 eq) over 20-25 min. The resulting solution was stirred for 1 h allowing ice bath to melt and reaction to gradually assume rt. Additional methylene chloride was added and the solution was washed with brine, dried and evaporated.

Provenance & Evidence