Diisopropylethylamine → 7-formyl-1-methyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide

Participants

Reaction Conditions

Reaction Steps

1.45 g 7-formyl-1-methyl-1H-indole-2-carboxylic acid (salt with N-methyl-morpholine) are dissolved in 8 ml N,N-dimethylformamide and combined with 2.72 g O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (HATU), 2.45 ml N,N-diisopropyl-ethylamine (DIEA) as well as 324 mg 1-hydroxy-7-azabenzotriazole (HOAT). The mixture is left for 15 minutes at ambient temperature with stirring and then 1.47 g N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulphonamide hydrochloride are added. The reaction is heated to 50° C. for 12 hours and then divided between water and ethyl acetate. The organic phase is washed successively with 1 N hydrochloric acid, water and saturated aqueous sodium chloride solution and dried on magnesium sulphate. After elimination of the solvents in vacuo the residue is chromatographed on silica gel with cyclohexane/ethyl acetate (70:30 to 20:80).

Provenance & Evidence