Triethylamine → 4-(2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4-yl)-1-methylpiperazin-2-one

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (80 mg, 0.157 mmol) and 1-methylpiperazin-2-one (17.94 mg, 0.157 mmol) in NMP (1.0 mL), followed by Et3N (65.6 μL, 0.472 mmol, Aldrich). The reaction was stirred and heated in a Initiator microwave reactor at 100° C. for 30 min. Then aq. NaOH (5 M, 0.3 mL) was added and the reaction was heated in microwave at 100° C. for 20 min. The mixture was purified with RP-HPLC (eluent: 10-60% MeCN in water with 0.1% TFA) and the fractions containing the product were combined and concentrated to remove AcCN. The remaining mixture was neutralized with sat. NaHCO3 and extracted with CHCl3/iPrOH (4:1). The combined organic layers were dried, filtered and concentrated to give 4-(2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4-yl)-1-methylpiperazin-2-one (30.0 mg, 0.069 mmol, 44.1%) as a light yellow solid. MS (ESI, pos. ion) m/z: 433.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.88 (1H, br. s.), 9.10 (1H, s), 8.30 (1H, d, J=6.1 Hz), 8.23 (1H, d, J=2.7 Hz), 7.60-7.73 (2H, m), 7.56 (1H, d, J=8.4 Hz), 6.69 (1H, d, J=6.1 Hz), 4.40 (2H, br. s.), 3.93 (2H, br. s.), 3.75 (1H, dq, J=13.3, 6.5 Hz), 3.51 (2H, t, J=5.2 Hz), 2.97 (3H, s), 1.25 (6H, d, J=6.8 Hz), 1.24 (3H, s).

Provenance & Evidence