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

Participants

Reaction Conditions

Reaction Steps

2-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (145 mg, 328 μmol) was dissolved in toluene (3 mL) and copper (I) iodide (3.29 mg, 36.7 μmol), sodium iodide (98.2 mg, 655 μmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (11.9 mg, 83.6 μmol) added. The mixture was degassed with bubbling nitrogen, then sealed and the mixture heated at to 110° C. After 15 h, 5-chloro-1H-indazole (50 mg, 328 μmol) and potassium phosphate tribasic (146 mg, 688 μmol) were added, the mixture degassed again, and the mixture sealed and the mixture heated at for an additional 24 h. The mixture was cooled, filtered the filtrates concentrated and purified by chromatography (silica, 24 g Analogix column, 0-40% ethyl Acetate in hexanes to give 2-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (124 mg, 74%) as a solid. MS (M+H)+=515; 1H NMR (CDCl3) d: 9.19 (s, 1H), 8.52 (d, J=8.9 Hz, 1H), 8.37 (s, 1H), 8.24 (s, 1H), 7.89 (s, 1H), 7.81-7.85 (m, 1H), 7.47 (dd, J=8.9, 1.9 Hz, 1H), 5.73 (s, 2H), 3.81 (s, 2H), 3.60 (dd, J=8.8, 7.6 Hz, 2H), 1.54 (s, 6H), 0.91-1.01 (m, 2H), −0.02 (s, 9H)

Provenance & Evidence