Hydrochloric Acid → 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide hydrochloride

Participants

Reaction Steps

2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (35 mg, 0.06 mmol) was dissolved in dichloromethane (1.6 ml) and cooled in ice bath. Trifluoroacetic acid (0.8 ml) was slowly added and the reaction was stirred at room temperature for 2 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1 ml). Ethylenediamine (0.25 ml, 3.7 mmol) was added and the mixture was stirred for 18 h. Water and then ethyl acetate were added to the mixture. The layers were separated and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane). The product thus isolated was dissolved in methanol/dichloromethane and treated with 4 eq of 4 M HCl in 1,4-dioxane. Evaporation of the solvent provided a solid which was dried under high vacuum to afford 18 mg (62%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide hydrochloride. MS: (M+H)+=444; mp=281-283° C. 1H NMR (300 MHz, DMSO-d6) δ: 10.17-10.33 (m, 1H), 9.08 (s, 1H), 8.44 (d, J=3.0 Hz, 1H), 8.26 (d, J=7.9 Hz, 1H), 8.03-8.08 (m, 1H), 7.34 (d, J=10.6 Hz, 1H), 4.94-5.05 (m, 2H), 4.14-4.30 (m, 1H), 3.66-3.77 (m, 2H), 2.89 (d, J=4.5 Hz, 6H), 1.24 (d, J=6.8 Hz, 6H).

Provenance & Evidence