Trimethylsilylacetylene → 4-{2-ethoxy-6-[2-(trimethylsilyl)ethynyl]-1H-1,3-benzodiazol-1-yl}pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(6-bromo-2-ethoxy-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (270 mg, 0.74 mmol) in piperidine (1.8 mL) was introduced tetrakis(triphenylphosphine)palladium(0) (69 mg, 0.06 mmol), copper(I) iodide (11 mg, 0.06 mmol) and ethynyltrimethylsilane (0.53 mL, 3.71 mmol). The reaction mixture was warmed to 65° C. for 3 hr. After cooling to RT, the reaction mixture was re-treated with further tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.01 mmol), copper(I) iodide (5 mg, 0.03 mmol), ethynyltrimethylsilane (0.20 mL, 1.4 mmol) and warmed to 65° C. for an additional 2 hr. The reaction mixture was concentrated in vacuo and the residue re-dissolved in DCM (10 mL) and re-evaporated to dryness in vacuo (this procedure was repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 2-8% gradient of methanol) furnished the title compound as an off-white solid: 1H NMR (250 MHz, DMSO) delta −0.07-0.07 (9 H, m), 1.21 (3H, t, J=7.01 Hz), 4.40 (2H, q, J=7.06 Hz), 6.65-6.81 (1H, m), 6.88 (2H, br. s.), 7.06 (1H, dd, J=8.15, 1.60 Hz), 7.20 (1H, d, J=8.22 Hz), 7.98 (1H, d, J=1.22 Hz), 8.12-8.25 (1H, m); LCMS: m/z=+352.45 (M+H)+.

Provenance & Evidence