Ethylenediamine → 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Participants

Reaction Steps

In a 25 mL round-bottom flask, 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (40 mg, 0.073 mmol) and TFA (0.60 ml, 7.8 mmol) were combined with dichloromethane (2 ml) to give an orange solution. The reaction mixture was stirred at room temperature for 2.5 h then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (2 mL) and ethylenediamine (0.40 ml, 5.9 mmol) was added. The reaction mixture was stirred at room temperature for 18 h then concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was purified by trituration (dichloromethane/heptane) to afford 17 mg (55%) of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as an off-white solid. MS: [M+H]+=417; 1H NMR (300 MHz, DMSO-d6) δ: 12.68 (br. s., 1H), 9.00 (s, 1H), 8.44 (s, 1H), 8.32 (d, J=8.7 Hz, 1H), 7.89 (d, J=1.5 Hz, 1H), 7.27 (dd, J=10.6, 1.5 Hz, 1H), 4.31 (dt, J=13.5, 7.0 Hz, 1H), 4.19 (s, 3H), 3.45 (dd, J=9.3, 5.8 Hz, 3H), 3.36 (dd, J=9.8, 5.3 Hz, 1H), 3.20 (s, 3H), 1.22 (d, J=6.8 Hz, 3H).

Provenance & Evidence