Acetic Anhydride → 5-amino-8-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

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Reaction Steps

Sodium hydride (60% suspension in mineral oil, 303 mg, 7.59 mmol) was added in one portion, under argon atmosphere, to a mixture of 4-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbonitrile (658 mg, 1.81 mmol) in anhydrous DMF (10 mL) and the resulting mixture was stirred at RT for 30 min. Anhydrous Ac2O (2.56 mL, 27.1 mmol) was added dropwise, over a period of 35 min, and the reaction mixture was stirred for additional 10 min. The resulting mixture was quenched with NH4Cl (sat'd aq, 50 mL), and extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×10 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was dissolved in MeOH (15 mL), and hydrazine hydrate (0.877 mL, 18.08 mmol) was added dropwise. The resulting mixture was heated at 85° C. in a microwave reactor for 50 min. The solvent was evaporated under reduced pressure and water was added to the residue. The resulting mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (3×10 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (DCM/MeOH) to afford 800 mg of 5-amino-8-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one.

Provenance & Evidence