Piperidine → (2R)-4-[1-(4-amino-1,3,5-triazin-2-yl)-2-cyclopropyl-1H-1,3-benzodiazol-6-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol

Participants

Reaction Conditions

Reaction Steps

To a microwave vessel was added 4-(6-bromo-2-cyclopropyl-1,3-benzodiazol-1-yl)-1,3,5-triazin-2-amine (0.3 g, 0.91 mmol) followed by piperidine (2.5 mL), tetrakis(triphenylphosphine)palladium(0) (104.68 mg, 0.09 mmol), copper(I) iodide (17.25 mg, 0.09 mmol) and (2R)-2-(1,3-thiazol-2-yl)but-3-yn-2-ol (0.28 g, 1.81 mmol). The reaction was capped and stirred in the microwave at 95° C. for 25 minutes (55 W). The reaction mixture was cooled to RT and concentrated in vacuo. The residue was re-dissolved in EtOAc and re-evaporated in vacuo (twice). The crude residue was subjected to column chromatography (Biotage, 0-8% methanol gradient in DCM) and the partially purified product triturated with a mixture of EtOAc/heptane to give the title compound as a beige solid: 1H NMR (DMSO, 500 MHz) delta 1.06-1.20 (4H, m), 1.89 (3H, s), 3.24-3.29 (1H, m), 7.04 (1H, s), 7.30 (1H, dd, J=8.2, 1.4 Hz), 7.53 (1H, d, J=8.2 Hz), 7.69 (1H, d, J=3.2 Hz), 7.78 (1H, d, J=3.2 Hz), 8.05 (1H, s), 8.09 (1H, s), 8.29 (1H, s), 8.68 (1H, s); LC-MS: m/z=+400 (M+H)+.

Provenance & Evidence