Triethylamine → 4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,5,6,7,8,9-hexahydro-1,4a,7-triaza-benzocyclohepten-9-yl)-benzamide

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Reaction Steps

To a solution of 0.040 g (0.199 mmol) of 4amino-5-chloro-2-methoxy-benzoic acid dissolved in 5 mL of anhydrous dimethylformamide was added 0.06 mL (0.43 mmol) of triethylamine, 0.077 g (0.20 mmol) of O-(benzotriazol-1-yl)-N,N,N′N,′-tetramethyluroniumhexafluorophosphate (HBTU). The resulting mixture was stirred at room temperature for 5 min and added slowly at −10° C. to a solution of 0.090 g (0.21 mmol) of (+/−)-9-amino-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-5H-1,4a,7-triaza-benzocyclohepten-4-one dihydrobromide (2:1) dissolved in a mixture of 5 mL of anhydrous dimethylformamide and 0.09 mL (0.64 mmol) of triethylamine. The resulting mixture slowly increases to room temperature and was stirred for 16 hours. After evaporation, the reaction mixture was diluted in dichloromethane and a saturated aqueous solution of sodium carbonate. The organic phase was washed saturated aqueous sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 97/3/0.3 to afford 0.022 g (23%) of the pure product as a powder.

Provenance & Evidence