Ethylenediamine → 2-(6-chloro-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Steps

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (154 mg, 0.23 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.72 ml, 9.35 mmol) was added. The orange reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (1.2 ml) and ethylenediamine (1.0 ml, 14.8 mmol) was added. The solution was stirred at room temperature for 1.5 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washing with water (hot), ethyl acetate and dichloromethane then dried under high vacuum to afford 37 mg (33%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white powder. MS: (M+H)+=463; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.70 (br. s., 1H), 9.15 (s, 1H), 8.73 (d, J=8.7 Hz, 1H), 8.47 (t, J=7.4 Hz, 2H), 7.98 (s, 1H), 7.27 (d, J=8.7 Hz, 1H), 4.47-4.84 (m, 3H), 4.18 (s, 3H), 4.02-4.32 (m, 2H), 3.86 (br. s., 1H), 1.42 (d, J=4.5 Hz, 3H).

Provenance & Evidence