Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-fluoro-1,2-dimethyl-propyl)-amide

Participants

Reaction Steps

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-fluoro-1,2-dimethyl-propyl)amide (93 mg, 0.176 mmol) was dissolved in dichloromethane (0.9 ml) and trifluoroacetic acid (0.54 ml, 7.0 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.9 ml) and ethylenediamine (0.7 ml, 10.5 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and extracted with dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-6% MeOH) then triturated with ethyl acetate to afford 34 mg (46%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-fluoro-1,2-dimethyl-propyl)-amide as a light yellow powder. MS: (M+H)+=399; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.90 (br. s., 1H), 9.12 (s, 1H), 8.45-8.54 (m, 2H), 8.25 (d, J=9.8 Hz, 1H), 7.68 (dd, J=9.8, 2.3 Hz, 1H), 7.09 (td, J=9.1, 2.3 Hz, 1H), 4.30-4.48 (m, 1H), 4.15 (s, 3H), 1.29-1.52 (m, 9H).

Provenance & Evidence