Sodium Hydroxide → 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine

Participants

Reaction Steps

A solution of 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.35 g, 0.56 mmol) in TFA (3.5 mL) was heated in a Biotage microwave at 100° C. for 30 min. The reaction was cooled to RT. TFA was removed in vacuo and the residue was washed with Et2O (7 mL) to get the crude product (250 mg), which was used in next step without further purification. MS (ESI, pos. ion) m/z: 506.1 (M+1). To a solution of crude 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (0.25 g, 0.442 mmol) in 1,4-dioxane (2.5 mL) was added 10% aq NaOH (1.3 mL) and the reaction was heated at 100° C. for 2 h. The mixture was treated with ice cold water (10 mL), resulting a white precipitate. The precipitate was filtered and washed with ice cold water (˜10 mL) and dried under vacuum. The solid was purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in H2O with 0.01% TFA) to give 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (30 mg, 17.5%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 11.96 (s, 1H), 9.05 (d, J=1.2 Hz, 1H), 8.25 (d, J=2.8 Hz, 1H), 7.76 (dd, J=8.4, 1.6 Hz, 1H), 7.69-7.65 (m, 2H), 7.64 (d, J=8.4 Hz, 1H), 7.46 (t, J=7.2 Hz, 2H), 6.70 (s, 2H), 6.54 (d, J=8 Hz, 1H), 5.61-5.55 (m, 1H), 1.52 (d, J=5.6 Hz, 6H).

Provenance & Evidence