Dimethylformamide → 6-(5,7-Dichloro-2,3-dihydro-1h-indol-1-yl)-4-(1-ethylpropyl)-4,5-dihydro-5-oxo-2-pyrazinecarbonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 5-bromo-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-2(1H)-pyrazinone (Example 507) (100 mg, 0.23 mmol), zinc cyanide (32 mg, 0.28 mmol), and tetrakis(triphenylphosphine)palladium(0) (32 mg, 25 μmol) in dimethylforamide (3 ml) was degassed with nitrogen and heated to 175° C. in a microwave for 5 min. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (5 mL×2). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a crude residue. Purification by HPLC (reverse phase C18, 95% water in acetonitrile containing 0.1% trifluroacetic acid to 5% water in acetonitrile containing 0.1% trifluroacetic acid, flow rate 18 ml/min, retention time 38.4 min) gave the product (18 mg, 21%) as a yellow solid. mp 197–199° C.; 1H NMR (300 MHz, CDCl3): δ 7.27 (s, 1 H), 7.19 (d, J=2.2 Hz, 1 H), 7.14 (d, J=1.8 Hz, 1 H), 4.82–4.77 (m, 1 H), 4.33 (t, J=7.9 Hz, 2 H), 3.15 (t, J=7.7 Hz, 2 H), 1.92–1.78 (m, 2 H), 1.75–1.60 (m, 2 H), 0.89 (t, J=7.3 Hz, 6 H); HRMS (ESI) calcd for C18H19N4OCl2 (M+H)+: 377.0936; Found m/z 377.0910.

Provenance & Evidence