proline dl-form → 1-[2-indol-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

Participants

Reaction Conditions

Reaction Steps

DMSO (3 mL) was added to a mixture of copper iodide (10 mg; 0.05 mmol), d,1-proline (12 mg; 0.10 mmol), potassium carbonate (111 mg; 0.79 mmol), and 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (150 mg; 0.36 mmol). Indole (327 mg; 2.91 mmol) was added and the resulting mixture was stirred at 100° C. (oil bath) for 24 hrs. TLC analysis (25% EtOAc/hexanes) shows a new more-polar product. The reaction mixture was poured into 50 mL of saturated sodium bicarbonate solution and extracted with EtOAc (2×30 mL). The organic layers were combined, washed with brine, dried over MgSO4, and concentrated to give a yellow oil. Chromatography (SiO2; 0-15% EtOAc in hexanes) gives 1-[2-indol-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (61%; ms=449 [M+H]) as a light brown oil. Following general procedures described in these Examples, the SEM group was removed to give 1-(2-Indol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one (53%; MS=319 [M+H]; 1H NMR (DMSO): δ 8.83 (s), 8.64 (s), 8.48 (d, br), 8.11 (d, br), 7.69 (d), 7.31 (t), 7.21 (t), 6.83 (d) ppm; MP: 205-207° C.).

Provenance & Evidence