Trifluoroacetic acid → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclohexyl)-amide

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Reaction Steps

The more polar, diastereomer A of (3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester (53 mg, 101 μmol) was dissolved in dichloromethane (5 mL) and treated with TFA (1.19 g, 803 μL, 10.4 mmol), the light yellow solution became a bright red-orange solution, stirring continued for 18 h at room temperature. Solvents were evaporated and the residue dissolved in dichloromethane/MeOH, adsorbed on silica gel and purified by chromatography (25 g column, 50 μm from Thomson, 0-10% MeOH containing 10% ammonium hydroxide in dichloromethane, 10 min gradient) to give an off white solid that was sonicated in MeOH and allowed to stand to promote complete solid formation. The solid was separated by decanting the mother liquor and dried under high vacuum to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclohexyl)-amide (diastereomer A) (27 mg, 63%) as an off-white solid. MS (M+H)+=424; 1H NMR (DMSO-d6) δ: 9.05 (s, 1H), 8.38-8.49 (m, 2H), 8.06 (d, J=7.9 Hz, 1H), 7.99 (s, 1H), 7.33 (d, J=10.2 Hz, 1H), 4.16 (s, 3H), 3.91 (d, J=4.2 Hz, 1H), 3.32 (br. s., 1H), 3.15 (s, 1H), 2.22 (d, J=11.0 Hz, 1H), 2.04 (d, J=11.7 Hz, 1H), 1.79 (br. s., 1H), 0.98-1.24 (m, 3H).

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