Diisopropylethylamine → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-methyl-5-phenyl-1H-pyrrole-2-carboxamide

Participants

Reaction Steps

To a solution of (R)-(+)-3-aminoquinuclidine dihydrochloride (0.831 g, 4.17 mmol) in 55 mL of dry THF is added DIEA (2.08 mL, 11.9 mmol). After allowing the mixture to stir under nitrogen for 15 min, the product from Step 152c (0.800 g, 3.98 mmol) is added. The mixture is allowed to stir for another 15 min, cooled in an ice bath, and HATU (1.59 g, 4.17 mmol) is added. The reaction mixture is stirred on an ice bath for 0.5 h, then at rt for an additional 2 h. The mixture is diluted with 60 mL CH2Cl2, washed with 50 mL of 1N NaOH and 50 mL of satd NaHCO3 solution, dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash column chromatography (10% EtOAc, 1% NH4OH in CH2Cl2) to give 0.383 grams of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-methyl-5-phenyl-1H-pyrrole-2-carboxamide (31%) as a white solid. MS for C19H23N3O (ESI) (M+H)+ m/z 310.3.

Provenance & Evidence