Water → tert-butyl methyl[2-({[3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-thienyl]carbonyl}amino)ethyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl (2-aminoethyl)(methyl)carbamate (158 μl; 154 mg; 0.88 mmol) in anhydrous toluene (3 mL) placed in a sealed tube under nitrogen was added a solution of trimethylaluminum (354 μl; 2 M; 0.71 mmol) in toluene. The colorless solution was stirred at 25° C. for 1 h, before 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methyl ester (55 mg; 0.18 mmol) was added and the resulting yellow suspension was heated to 105° C. overnight. The reaction mixture was allowed to cool down before water (0.1 mL) was added. The resulting gray suspension was stirred at 25° C. for 2 h, diluted with methanol and purified by chromatography on a SP1 Biotage system, using hexane and ethyl acetate as eluents to afford crude tert-butyl methyl[2-({[3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-thienyl]carbonyl}amino)ethyl]carbamate as a white solid. The solid was suspended in methanol (1 mL) in a 5 mL flask with magnetic stir bar. To the white suspension was added hydrochloric acid (0.21 mL, 2.0N in diethyl ether, 0.42 mmol). The resulting solution was stirred at 25° C. overnight and the resulting precipitate was collected by filtration. The precipitate was purified using preparative HPLC to afford 3-(7H-Pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid (2-methylamino-ethyl)-amide (1 mg, 2%) as a brown solid. 1H NMR (MeOH-d4) 8.55 (d, J=5.5 Hz, 1H), 8.40 (s, 1H), 7.66 (d, J=5.2 Hz, 1H), 7.29 (d, J=3.7 Hz, 1H), 6.61 (d, J=3.3 Hz, 1H), 3.73-3.67 (m, 2H), 3.34-3.28 (m, 2H), 2.75 (s, 3H); MS (m/z) 317 [M+H]+.

Provenance & Evidence