Triethylamine → (+/-)-2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,5,6,7,8,9-hexahydro-1,4a,7-triaza-benzocyclohepten-9-yl)-nicotinamide

To a solution of 0.040 g (0.26 mmol) of 6-methoxy-pyridine-2-carboxylic acid dissolved in 8 mL of anhydrous dichloromethane was added 0.11 mL (0.79 mmol) of triethylamine, 0.050 g (0.26 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.035 g (0.26 mmol) of 1-hydroxybenzotriazole. The resulting mixture was stirred at room temperature for 10 min and added slowly at −10° C. to a solution of 0.110 g (0.26 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 17 mL of anhydrous dichloromethane and 0.15 mL (1.05 mmol) of triethylamine. The resulting mixture was stirred at −10° C. for 1 hour and at room temperature for 16 hours. After addition of water, extraction with dichloromethane; the reaction mixture was washed with 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 90/10/1 to afford 0.100 g (90%) of the pure product as a powder.

1. stirringThe resulting mixture was stirred at −10° C. for 1 hour and at room temperature for 16 hours
2. washthe reaction mixture was washed with saturated aqueous sodium chloride
3. dry with materialdried over sodium sulfate
4. customevaporated to dryness
5. customThe residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 90/10/1

ORD record

ord-824c18e61e1b4202b40eee4d3e631ce8

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507475B2