Ethylenediamine → 2-(1,5,5-Trimethyl-4,5,6,7-tetrahydro-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

Participants

Reaction Steps

In a round-bottomed flask, 5-(2-trimethylsilanyl-ethoxymethyl)-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-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 (112 mg, 0.19 mmol) was dissolved in dichloromethane (0.9 ml) and trifluoroacetic acid (0.6 ml, 7.5 mmol) was added. The yellow solution was stirred at room temperature for 2.5 h then concentrated. The residue was redissolved in dichloromethane (0.9 ml) and ethylenediamine (0.8 ml, 11.4 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 47 mg (51%) of 2-(1,5,5-Trimethyl-4,5,6,7-tetrahydro-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)+=461; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.61 (br. s., 1H), 8.94 (s, 1H), 8.27-8.41 (m, 2H), 4.43-4.80 (m, 3H), 3.94-4.24 (m, 2H), 3.80 (s, 3H), 3.72-3.91 (m, 1H), 2.89 (d, J=15.9 Hz, 1H), 2.59-2.71 (m, 3H), 1.59 (t, J=6.2 Hz, 2H), 1.40 (dd, J=6.8, 3.0 Hz, 3H), 1.00 (s, 6H).

Provenance & Evidence