2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → 2-(6-chloro-1H-indazol-3-yl)-N-isopropyl-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-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (289 mg, 700 μmol) and 6-chloro-3-(tributylstannyl)-1H-indazole (see Example 4, 2.01 g, 4.55 mmol) in DMF at 20° C. was added copper(I) iodide (25.1 mg, 280 μmol) and then the mixture degassed with bubbling Argon for 15 min. Tetrakis(triphenylphosphine)palladium(0) (80.9 mg, 70.0 μmol) was added then the reaction mixture was heated to 80° C. After 15 h the mixture was cooled and diluted with ethyl acetate and saturated aqueous saturated ammonium chloride solution. The organic layer was separated and washed with brine, then dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by chromatography (silica, 40 g Analogix column, 20-50% ethyl acetate in hexanes, gradient over 15 min) to give 2-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.080 g) as a light brown oil. This was approximately 75% pure by 1H NMR with a single, major impurity tentatively assigned as 6,6′-dichloro-1H,1′H-[3,3′]biindazolyl and was used directly in the next step without further purification. MS (M−H)−=483; 1H NMR (CDCl3) δ: 8.41 (s, 1H), 8.35 (s, 1H), 8.07 (br. s, 1H), 7.64-7.77 (m, 2H), 7.52 (s, 1H), 7.16 (d, J=8.7 Hz, 1H), 5.64 (s, 2H), 4.23-4.47 (m, 1H), 3.45-3.58 (m, 2H), 1.34 (d, J=6.4 Hz, 6H), 0.93 (s, 2H), −0.05 (s, 9H)

Provenance & Evidence