Tetrabutylammonium Fluoride → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide

Participants

Reaction Steps

To a 20 ml vial containing 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide (51 mg, 0.085 mmol) dissolved in THF (1 ml) was added TBAF (1.0 M in THF, 1.0 ml, 1.0 mmol). The vial was backfilled with nitrogen then sealed and placed in heat block at 80° C. for 3 h. The reaction was cooled to room temperature, quenched with acetone (2 ml) and sat'd NaHCO3 (20 ml). The mixture was stirred for 1 h then extracted with EtOAc and the organics washed with brine. The aqueous was again extracted with EtOAc and the organics washed with brine. The organics were combined, dried over MgSO4, filtered and concentrated. The crude was dissolved in MeOH and EtOAc, supported on Celite, and purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane to 10% MeOH in EtOAc. The appropriate fractions were combined and concentrated. The solid was triturated with dichloromethane, Et2O, and hexanes to isolate 11 mg (29%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide as a white solid. LC-MS (M+H)+=470; 1H NMR (300 MHz, DMSO-d6) δ: 12.87 (br. s., 1H), 9.10 (s, 1H), 8.34-8.54 (m, 3H), 7.68 (dd, J=9.8, 1.8 Hz, 1H), 7.11-7.26 (m, 5H), 6.97 (td, J=9.1, 1.9 Hz, 1H), 4.60 (br. s., 1H), 4.16 (s, 3H), 3.61 (s, 2H), 2.82-2.97 (m, 1H), 2.58-2.75 (m, 2H), 2.29-2.44 (m, 2H), 1.75 (br. s., 1H).

Provenance & Evidence