Reaction Steps
An orange solution of tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylate (38.6 mg, 0.056 mmol) and aq. NaOH (2.0 M, 0.1 mL, 0.200 mmol) in dioxane (1.0 mL) was heated at 100° C. for 30 min. Additional aq. NaOH (2.0 M, 0.1 mL, 0.200 mmol) was added, and the resulting mixture was stirred at 100° C. for 1.5 h. The mixture was then concentrated in vacuo, and the residue was taken up in HCl (4.0 M in dioxane; 1.0 mL, 4.00 mmol). The resulting yellow-orange mixture was stirred at 25° C. for 1 h, diluted with H2O (4 mL) and 1 N aq NaOH (3.5 mL). The resulting mixture was partitioned between DCM (30 mL) and saturated aq NaHCO3 (20 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (20 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to provide crude 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-N-(piperidin-3-yl)-1,3,4-thiadiazol-2-amine as a light-yellow solid, which was taken up in DMSO (2.0 mL) and purified by reverse phase HPLC (10-100% AcCN/H2O+0.1% TFA) to provide 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-N-(piperidin-3-yl)-1,3,4-thiadiazol-2-amine 2,2,2-trifluoroacetate (12.0 mg, 0.022 mmol, 39%) as a yellow oil: MS (ESI, pos. ion) m/z: 435.2 (M+1). 1H NMR (400 MHz, MeOH-d4) δ ppm 11.38 (br s, 1H), 8.80 (d, J=1.2 Hz, 1H), 7.98 (s, 1H), 7.75-7.79 (m, 1H), 7.71-7.75 (m, 1H), 7.54 (d, J=8.6 Hz, 1H), 7.43 (d, J=7.4 Hz, 1H), 6.66 (d, J=8.2 Hz, 1H), 5.53 (dt, J=12.2, 6.1 Hz, 1H), 4.07-4.16 (m, 1H), 3.68 (dd, J=12.2, 3.6 Hz, 1H), 3.34-3.35 (obsc m, 1H), 3.09-3.15 (m, 1H), 3.02-3.08 (m, 1H), 2.18-2.27 (m, 1H), 2.10 (dt, J=15.0, 5.1 Hz, 1H), 1.83-1.92 (m, 1H), 1.73-1.82 (m, 1H), 1.49-1.51 (m, 3H), 1.49 (s, 3H).
