Trifluoroacetic acid → 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine

Participants

Reaction Steps

To a mixture of tert-butyl (3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (0.49 g, 0.8 mmol) in DCM (10 mL) was added TFA (4 mL) at 0° C. The reaction was stirred for 2 h at RT. The solvent was then removed in vacuo and the residue was triturated with Et2O to give 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (0.23 g, 56.2%). MS (ESI, pos. ion) m/z: 506.1 (M+1). To a solution of 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (0.23 g, 0.45 mmol) in 1-4-dioxane (10 mL) was added 10% aq NaOH (5 mL) and the reaction was heated at 100° C. for 2 h. The reaction was quenched with ice cold H2O to give a pale yellow precipitate. The precipitate was filtered, washed with ice cold H2O and dried under vacuum. The crude product was purified with preparative HPLC (eluent: 20-80% AcCN in H2O with 0.1% TFA) to give 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (45 mg, 28.3%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H NMR (DMSO-d6, 400 MHz): δ 11.81 (s, 1H), 9.19 (s, 1H), 8.20-8.18 (m, 2H), 7.92 (dd, J=8.4, 1.2 Hz, 1H) 7.86 (brs, 2H), 7.63 (s, 1H), 7.47 (d, J=8.4 Hz, 1H), 4.32-4.29 (m, 1H), 1.29 (d, J=6.4 Hz, 6H).

Provenance & Evidence