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

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.

1. temperatureThe resulting mixture slowly increases to room temperature
2. stirringwas stirred for 16 hours
3. customAfter evaporation
4. additionthe reaction mixture was diluted in dichloromethane
5. washThe organic phase was washed saturated aqueous sodium chloride
6. dry with materialdried over sodium sulfate
7. customevaporated to dryness
8. customThe residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 97/3/0.3

ORD record

ord-442db1050c844183aeae6d62081b8b39

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507476B2