Cyanide synthesis

A stirred mixture of (6-bromo-4H-benzo[d][l,3]oxazin-2-yl)-(R)-indan-1-yl-amine

(2.0 g, 5.83 mmol), zinc cyanide (1.03 mg, 8.77 mmol) and Pd(PPh3)4 (673mg, 0.58 mmol) in N,N-dimethylformamide (20 ml) was heated at 160°C for 15 min in a microwave reactor. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (2 x 70 ml). The combined organic layers were washed with brine (2 x 40 ml), dried (magnesium sulfate) and evaporated. The crude product was purified by flash chromatography (ethyl acetate/ heptane) on silica gel to yield the title compound as light yellow foam (693 mg, 41%).


Patent reference: WO2010026110 (Roche)