2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

2-Bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (184 mg, 446 μmol) and 1-methyl-3-(tributylstannyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (293 mg, 714 μmol) were dissolved in DMF (2.5 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (25.8 mg, 22.3 μmol) and CuI (17.0 mg, 89.2 mmol) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 2.5 h. The reaction mixture was concentrated under high vacuum and the residue was purified by chromatography (40 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min) to give N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (68 mg, 150 μmol, 34%) as a light yellow solid. MS (M+Na)+=477; 1H NMR (CDCl3) δ: 9.06 (s, 1H), 8.28 (s, 1H), 8.13 (d, J=8.3 Hz, 1H), 5.68 (s, 2H), 4.44 (dq, J=14.5, 6.6 Hz, 1H), 3.89 (s, 3H), 3.47-3.64 (m, 2H), 3.04 (t, J=7.0 Hz, 2H), 2.62-2.86 (m, 4H), 1.34 (d, J=6.8 Hz, 6H), 0.86-0.96 (m, 2H), −0.06 (s, 9H).

Provenance & Evidence