Acetamide → HCID 44438909, compound

Participants

Reaction Conditions

Reaction Steps

Argon was bubbled through a suspension of 1-[3-(3-bromobenzyloxy)-phenyl]-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine (1, 25 mg, 0.056 mmol), potassium carbonate (15 mg, 0.109 mmol), copper(I) iodide (10 mg, 0.052 mmol), acetamide (40 mg, 0.68 mmol) and N,N′-dimethylethylenediamine (5 mg, 0.057 mmol), in dioxane (0.5 ml) in a thick walled 5 ml microwave tube. The tube was sealed and heated to 170° C. for 2 hours using the CEM Discover microwave oven at a maximum power of 250 W. The reaction mixture was then partitioned between water (3 ml) and ethyl acetate (3 ml) and the aqueous layer was extracted with further ethyl acetate (2×3 ml). The combined organic extracts were washed with water (2×3 ml) and brine (3 ml) then evaporated in vacuo. The residues after evaporation were dissolved in methanol and loaded on to 1 g SCX cartridges, then eluted with methanol and methanol/ammonia (concentrated aqueous ammonia in methanol, 3% v/v). Fractions containing product were combined and evaporated to furnish N-{3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-phenyl}-acetamide as an off white solid (10 mg, 0.023 mmol, 42%, 85% pure). This was purified further using preparative mass directed HPLC purification (conditions) to afford 2 as an off white solid (6.3 mg, 0.015 mmol, 27%; (M+H)+ m/z 428.2; Retention Time; 2.87 min; 1H-NMR (D4-MeOH) δ 7.72 (1H, br t), 7.53 (1H, br d, J=8 Hz), 7.49 (1H, t, J=8 Hz), 7.43 (1H, d, J=5.1 Hz), 7.35 (1H, t, 7.8 Hz), 7.29 (1H, br t), 7.25-7.22 (2H, m), 7.17 (1H, dd, J=2.8, 8.2 Hz), 7.01 (1H, d, J=5.1 Hz), 5.21 (2H, s), 4.00 (1H, p, J=8.4 Hz), 2.55 (4H, m), 2.22 (1H, m), 2.15 (3H, s), 2.10-2.02 (1H, m).

Provenance & Evidence