Sodium hydride → 5-amino-8-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

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Reaction Conditions

Reaction Steps

Sodium hydride (60% suspension in mineral oil, 468 mg) was added portionwise, at RT, under argon atmosphere, to a solution of N-(5-cyano-2-methylsulfanyl-pyrimidin-4-yl)-acetamide (2.03 g, 9.75 mmol) in anhydrous DMSO (20 mL) and the resulting mixture was stirred at RT for 40 min. (3-Bromopropoxy)-tert-butyldimethylsilane (3.39 mL, 14.63 mmol) was then added dropwise over a period of 2 min at RT and the reaction mixture was stirred for 2 h. The resulting mixture was then heated at 85° C. for 2 h; a second portion of NaH (60% suspension in mineral oil, 78 mg) was then added and was followed after 30 min by (3-bromopropoxy)-tert-butyldimethylsilane (0.45 mL). The resulting mixture was heated at 85° C. for 1 h, cooled and quenched with water. The resulting mixture was extracted with EtOAc (3×50 mL); the combined organic layers were washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography to afford 800 mg (22% yield) of 5-amino-8-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one and 600 mg of uncyclized N-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-N-(5-cyano-2-methylsulfanyl-pyrimidin-4-yl)-acetamide which was converted in the title compound by treatment with lithium bis(trimethylsilyl)amide as described in Preparation 2 Step C.

Provenance & Evidence