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

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[6-bromo-2-(methoxymethyl)-1H-1,3-benzodiazol-1-yl]-1,3,5-triazin-2-amine (150 mg at 86% purity, 0.38 mmol) in piperidine (3 mL) was introduced tetrakis(triphenylphosphine)palladium(0) (22.2 mg, 0.02 mmol), copper(I) iodide (7.3 mg, 0.04 mmol) and (2R)-2-(1,3-thiazol-2-yl)but-3-yn-2-ol (118 mg, 0.77 mmol). The reaction was warmed to 70° C. for 1 hr. After cooling to RT, additional tetrakis(triphenylphosphine)palladium(0) (22.2 mg, 0.02 mmol) was introduced and the reaction mixture warmed to 70° C. for a further 1 hr. The reaction mixture was concentrated in vacuo and the residue purified by silica gel flash chromatography (DCM containing a 0-3% gradient of methanol) to furnish the title compound as a brown oil: 1H NMR (500 MHz, DMSO) delta 1.90 (3H, s), 5.10 (2H, s), 7.06 (1H, br. s.), 7.31-7.40 (1H, m), 7.64-7.73 (2H, m), 7.75-7.80 (1H, m), 8.02 (1H, br. s.), 8.08 (1H, br. s.), 8.30 (1H, s), 8.40-8.45 (1H, m), 8.65 (1H, s); LC-MS: m/z=+408.00 (M+H)+.

Provenance & Evidence