Sodium Iodide → N-(1-Hydroxy-2-methylpropan-2-yl)-2-(1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (140 mg, 316 μmol) in toluene (2 mL) was added copper (I) iodide (3.17 mg, 35.4 μmol), sodium iodide (94.7 mg, 631 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (11.5 mg, 80.5 μmol). The reaction mixture was sealed under nitrogen and the mixture heated at 110° C. for 15 h. To the mixture was added 1H-indazole (37.3 mg, 316 μmol) and potassium phosphate tribasic (141 mg, 663 μmol) then the reaction vessel was degassed, filled with nitrogen, and the mixture heated at in sealed tube at 110° C. for 15 h. The mixture was filtered, the cake washed with ethyl acetate, and the filtrate concentrated in vacuo Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-(1-Hydroxy-2-methylpropan-2-yl)-2-(1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (112 mg, 74%). 1H NMR (CDCl3) d: 9.21 (s, 1H), 8.58 (d, J=8.5 Hz, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 8.01 (s, 1H), 7.87 (d, J=8.1 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.31-7.41 (m, 1H), 5.73 (s, 2H), 3.81 (s, 2H), 3.55-3.66 (m, 2H), 1.55 (s, 6H), 0.89-1.04 (m, 2H), −0.02 (s, 9H).

Provenance & Evidence