Methyl iodide → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-methoxymethyl-3-methyl-butyl)-amide

Participants

Reaction Steps

In a 10 mL round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-hydroxymethyl-3-methyl-butyl)-amide (73 mg, 0.135 mmol) was dissolved in THF (1.4 ml) to give a colorless solution. The reaction was cooled in an ice bath and crushed KOH (76 mg, 1.35 mmol), 18-crown-6 (36 mg, 0.135 mmol), and iodomethane (9 μl, 0.135 mmol) were added successively. The reaction mixture was stirred at 0° C. for 1 h after which the ice bath was removed. The reaction mixture was stirred at room temperature for 2 h then diluted with dichloromethane (10 mL) and washed with aqueous ammonium chloride (10 mL), water (10 mL), and saturated sodium bicarbonate (10 mL). The organic layer was dried over Na2SO4 and concentrated. The crude material was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0%-70% EtOAc) to afford 38 mg (50%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-methoxymethyl-3-methyl-butyl)-amide as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ: 9.18 (s, 1H), 8.64 (s, 1H), 8.52 (dd, J=9.1, 5.3 Hz, 1H), 8.15 (d, J=9.4 Hz, 1H), 7.72 (dd, J=9.6, 2.1 Hz, 1H), 7.13 (td, J=9.1, 1.9 Hz, 1H), 5.73 (s, 2H), 4.41 (td, J=9.0, 5.1 Hz, 1H), 4.17 (s, 3H), 3.60 (t, J=7.9 Hz, 2H), 3.44-3.55 (m, 2H), 3.27 (s, 3H), 1.48-1.72 (m, 3H), 0.91 (d, J=6.0 Hz, 3H), 0.86 (d, J=6.0 Hz, 3H), 0.85 (t, J=7.6 Hz, 2H), −0.08 (s, 9H).

Provenance & Evidence