Diisopropylethylamine → 5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamine

Participants

Reaction Conditions

Reaction Steps

A solution of 2-amino-5-bromopyrazine (100 mg, 0.58 mmol) in N,N-dimethylformamide (6 mL) was treated with tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.01 mmol), N,N-diisopropylethylamine (250 μL, 1.43 mmol), lithium chloride (85 mg, 2.01 mmol), and 5,6-dihydro-2-(tributylstannyl)-4H-pyran (214 mg, 0.58 mmol). The resulting reaction mixture was heated at 120° C. for 4 h. After such time, the reaction was cooled to 25° C., treated with a saturated aqueous potassium fluoride solution (10 mL), and stirred at 25° C. overnight for 16 h. The solution was then diluted with methylene chloride (25 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 1/1 to 1/3 hexanes/ethyl acetate) afforded 5-(5,6-dihydro-4H-pyran-2-yl)-pyrazin-2-ylamine (25 mg, 25%) as a foam: EI-HRMS m/e calcd for C9H11N3O (M+) 177.0902, found 177.0906.

Provenance & Evidence