3-bromopyrazolo[1,5-a]pyrazine synthesis

Yield:53902-93-5 76%

Reaction Conditions:

with N-Bromosuccinimide;sodium hydrogencarbonate in N,N-dimethyl-formamide at 20; for 6 h;

Steps:

97.a

PREPARATION 97 3-(Tributylstannyl)pyrazolo[1,5-a]pyrazine [Show Image]a) 3-Bromopyrazolo[1,5-a]pyrazine Sodium hydrogen carbonate (6.06 g, 72.1 mmol) and N-bromosuccinimide (4.28 g, 24.0 mmol) were added sequentially to a suspension of pyrazolo[1,5-a]pyrazine-3-carboxylic acid (Preparation 90b, 3.92 g, 24.0 mmol) in N,N'-dimethylformamide (67 mL) and the mixture was stirred at room temperature. After 6 hours, the mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted with further ethyl acetate. The combined organic extract was dried (MgSO₄) and evaporated and the residue was purified by flash chromatography (4:1 hexanes/ethyl acetate) to give the title compound (3.60 g, 76%) as a cream coloured solid. LRMS (m/z): 198/200 (M+1)⁺.H NMR (250 MHz, DMSO-d₆) δ ppm 8.00 (d, 1H), 8.35 (s, 1H), 8.83 (dd, 1H), 9.11 (d, 1H).

References:

EP2397482,2011,A1 Location in patent:Page/Page column 103-104