Propyne → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-prop-1-ynylpyrrolo[1,2-a]pyrazine-3-carboxamide Tartrate

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Reaction Steps

To an argon purged mixture of dichlorobis(benzonitrile)palladium (II) (0.085 g, 0.22 mmol) and copper (I) iodine (0.124 g, 0.65 mmol) is added, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromopyrrolo[1,2-a]pyrazine-3-carboxamide (0.641 g, 1.8 mmol) and dioxane (20 mL). The suspension is sparged with argon, and diiopropylamine (0.30 mL, 1.5 mmol), tri tert-butyl phosphine (0.064 g, 0.32 mmol) and condensed propyne (excess) is added. The reaction vessel is quickly sealed and stirred at rt for 15 h at which point it is filtered through a plug of celite, concentrated to dryness, and the residue dissolved in CHCl3 (150 mL) that is washed with a solution containing 1:1 NH4OH/brine (5×35 mL). The crude oil is purified using preparative HPLC to give a yellow oil that is salted with d-tartaric acid, and crystallized from EtOH/Et2O to give a pale yellow solid. Yield 5%. HRMS (FAB) calcd for C18H20N4O+H 309.1715, found 309.1715.

Provenance & Evidence