Water → 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid [2-(3-fluorophenyl)-ethyl]-amide

Participants

Reaction Steps

To a solution of 3-fluorophenethylamine (130 μL; 134 mg; 0.97 mmol) in anhydrous toluene (3 mL) placed in a microwave tube under nitrogen was added a solution of trimethylaluminum (390 μL; 2.00 M; 0.77 mmol) in toluene. The colorless solution was stirred at 25° C. for 15 min, before 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid benzylamide (60 mg; 0.19 mmol), was added. The resulting green solution was stirred for 15 min under a flow of nitrogen, and microwaved to 120° C. for 30 min. The reaction mixture was allowed to cool down before water (0.1 mL) was added. The resulting beige suspension was stirred at 25° C. for 2 h, diluted with methanol and purified by chromatography on a SP1 Biotage system, using dichloromethane and methanol as eluents to afford 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid [2-(3-fluorophenyl)-ethyl]-amide (9 mg, 12%) as a white solid (HPLC: 98%, RT: 6.33 min). 1H NMR (DMSO-d6) 11.97 (br s, 1H), 11.37 (s, 1H), 8.48 (d, J=5.5 Hz, 1H), 8.38 (s, 1H), 8.33 (t, J=5.5 Hz, 1H), 7.75 (d, J=5.5 Hz, 1H), 7.37 (dd, J=3.7, 2.6 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.13-7.08 (m, 2H), 7.03 (td, J=8.1, 2.6 Hz, 1H), 6.45 (dd, J=3.7, 1.8 Hz, 1H), 3.53 (q, J=6.6 Hz, 2H), 2.90 (t, J=7.1 Hz, 2H); MS (m/z) 382 [M+H]+.

Provenance & Evidence