1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86650160, compound

Participants

Reaction Conditions

Reaction Steps

To a flask containing (+/−)-2-[3-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-prop-1-ynyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (395 mg, 0.83 mmol) was added copper iodide (79 mg, 0.41 mmol), and DBU (0.57 mL, 3.8 mmol) in dry dimethyl acetamide (4 mL). The mixture was vacuum degassed and the flask was wrapped with tin foil (protect from light) and heated to 130° C. and stirred for 5 hours. Additional copper iodide (110 mg) was added and the mixture was stirred for another 6 hours and then cooled to ambient with over-night stirring. The material was taken up in water (30 mL) and ethyl acetate (30 mL), transferred to a reparatory funnel and shaken. The organic phase was collected and shaken with an equal volume of brine. The aqueous phases were back extracted with ethyl acetate (2×25 ml), the organics combined, dried (MgSO4), filtered and stripped. The remainder was purified by preparative TLC eluting with 45% ethyl acetate in hexanes (develop plates in the dark). A less polar component was collected providing 23 mg of semi-pure trans-(+/−)-8-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-3,4,8a-triaza-as-indacene product. MS (M+H)+=477. Also 17 mg of a more polar cis-(+/−)-8-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-3,4,8a-triaza-as-indacene product was collected. MS (M+H)+=477.

Provenance & Evidence