2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-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 (124 mg, 301 μmol) and 1,5,5-trimethyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazole (see Example 13, 219 mg, 483 μmol.61) were dissolved in DMF (2.5 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (17.4 mg, 15.0 μmol) and CuI (5.39 mg, 60.2 μmol, Eq: 0.20) 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 (115 g column, 50 μm from Analogix, 0-70% EtOAc/hexanes, 30 min gradient) to give N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (113 mg, 227 μmol, 76%) as a light yellow solid. MS (M+Na)+=497; 1H NMR (CDCl3) δ: 9.08 (s, 1H), 8.28 (s, 1H), 5.68 (s, 2H), 4.38-4.56 (m, 1H), 3.86 (s, 3H), 3.50-3.59 (m, 2H), 2.80 (s, 2H), 2.65 (t, J=6.4 Hz, 2H), 1.69 (t, J=6.6 Hz, 2H), 1.36 (d, J=6.8 Hz, 6H), 1.07 (s, 6H), 0.88-0.96 (m, 2H), −0.06 (s, 9H).

Provenance & Evidence