Propargyl bromide → 2-[5-chloro-2-(10-prop-2-ynyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

Participants

Reaction Steps

2-[2-(10-Aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide (30 mg, 0.0667 mmol) was placed in acetone (3 mL) and cesium carbonate (65 mg, 0.200 mmol, 3.0 eq) was added followed by propargyl bromide (80% in toluene) (7.9 μL, 0.0734 mmol, 1.1 eq). The reaction was stirred at room temperature for 24 hours and was then concentrated under reduced pressure. The residue was taken up in CH2Cl2 (10 mL) and washed with water (10 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-10% MeOH/CH2Cl2 as the eluting solvent to obtain 2-[5-chloro-2-(10-prop-2-ynyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as an orange foam (30 mg, 92%). LCMS (m/e) 487 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.03 (s, 1H), 8.66 (d, 1H, J=8.5 Hz), 8.08 (s, 1H), 7.51-7.40 (m, 2H), 7.37 (d, 1H, J=2.2 Hz), 7.30-7.20 (m, 1H), 7.10-7.0 (m, 2H), 6.92 (s, 1H), 6.18 (bs, 1H), 3.37 (d, 2H, J=2.3 Hz), 3.03 (d, 3H, 4.9 Hz), 3.03-2.98 (m, 1H), 2.97-2.87 (m, 3H), 2.52-2.45 (m, 2H), 2.23-2.15 (m, 2H), 2.14 (t, 1H, J=2.3 Hz), 1.70-1.62 (m, 2H).

Provenance & Evidence