Chloroacetyl chloride → 7-{4-[2-(4-dimethylamino-piperidin-1-yl)-acetyl]-piperazin-1-ylmethyl}-1-methyl-1H-indole-2-carboxylic acid-(5-tert-butyl-3-methanesulphonylamino-2-methoxy-phenyl)-amide

Participants

Reaction Conditions

Reaction Steps

160 mg of 1-methyl-7-piperazin-1-ylmethyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulphonylamino-2-methoxy-phenyl)-amide are dissolved in 5 ml dichloromethane, combined with 100 μL N,N-diisopropyl-ethylamine (DIEA) and cooled to 0° C. Then 30 μl of chloroacetic acid chloride are added dropwise, the mixture is heated to ambient temperature and stirred for 1 hour. The solvent is eliminated in vacuo and the residue is taken up in 2 ml N,N-dimethylformamide. Then 65 mg potassium carbonate and 55 μl 4-dimethylamino-piperidine are added successively. The mixture is stirred for 12 hours at ambient temperature, divided between water and ethyl acetate and the organic phase is washed with saturated aqueous sodium chloride solution. After drying with magnesium sulphate the solvents are eliminated in vacuo and the residue is chromatographed on silica gel (dichloromethane/(methanol/conc. ammonia 9:1) 99:1 to 85:15).

Provenance & Evidence