Triethylamine → HCID 178471562, compound

Participants

Reaction Steps

To a suspension of 3.33 g (12.9 mmol) of N-(4-hydroxy-5-ethynyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropionamide in 64 mL of acetonitrile stirred under nitrogen was added 5.77 g (28.4 mmol) of BSA and the resulting mixture was stirred at 40° C. for 2 hours, then cooled to ambient temperature. To the resulting solution was added sequentially 5.58 g (12.9 mmol) of N-4-iodobenzoyl-L-glutamic acid diethyl ester, 2.6 g (25.8 mmol) of triethylamine, and a mixture of 0.114 g (0.65 mmol) of palladium(II) chloride and 0.338 g (1.29 mmol) of triphenylphosphine in 16 mL of acetonitrile. The resulting mixture was heated under reflux overnight (18 hours), after which time HPLC analysis of an aliquot indicated complete conversion of the (acetylenic) starting material. The mixture was cooled to ambient temperature and 2 mL of water was added. The resulting suspension was stirred for 30 minutes, filtered, and the precipitate washed with acetonitrile and dried, affording 6.15 g (85%) of N-[4-[2-[2-(2,2-dimethylpropionyl)amino-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl ]ethynyl]benzoyl]-L-glutamic acid diethyl ester as a tan solid. The melting point and NMR spectral data for the product were in agreement with data obtained on an authentic sample prepared by the procedure of Example 3.

Provenance & Evidence