Potassium Hydroxide → 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one (70 mg, 0.103 mmol) in THF (2 mL) followed by 1 M KOH (500 μL, 0.500 mmol). The mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 1 h, then cooled to RT. The mixture was diluted with H2O, and extracted with DCM. The combined organic layers were dried, filtered and concentrated to give the crude 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one. MS (ESI, pos. ion) m/z: 527 (M+1). A glass microwave reaction vessel was charged with the above crude compound (54 mg, 0.103 mmol) in TFA (1 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 30 min, then solvent was removed. The residue was purified with RP-HPLC to give 4-(6-(5-(5-amino-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one (10.0 mg, 0.025 mmol, 24%) as a light yellow solid. MS (ESI, pos. ion) m/z: 407 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.86 (1H, br. s.), 8.73 (1H, s), 8.48 (1H, s), 8.28 (1H, d, J=2.5 Hz), 8.05 (1H, s), 7.74 (1H, dd, J=8.5, 1.5 Hz), 7.53 (1H, d, J=8.4 Hz), 7.26 (3H, s), 4.23 (2H, s), 4.06 (2H, t, J=5.4 Hz), 3.60 (2H, t, J=5.5 Hz), 3.28 (1H, s), 2.96 (3H, s)

Provenance & Evidence