Potassium Iodide → Ammonium Acetate

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with a solution of N-((1S,3S,4R)-3-(2-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)ethylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide (0.350 g, 0.619 mmol) in 1-propanol (3.2 mL). DIPEA (0.324 mL, 1.86 mmol) and potassium iodide (0.154 g, 0.929 mmol) were added and the reaction was heated in a Biotage® microwave for about 10 h at about 180° C. EtOAc and water (10 mL each) were added to the reaction mixture and the layers were separated. The aqueous phase was extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/Et2NH (950/45/5) in DCM and the solvent was removed under reduced pressure. The solid was further purified by preparative HPLC (Table 1, Method w) to give to give N-((1S,3S,4R)-3-(2,3-dihydrodipyrrolo[2,3-b:2′,3′-d]pyridin-1(6H)-yl)-4-ethylcyclopentyl)cyclopropanesulfonamide with 30 mol % ammonium acetate as an excipient (0.099 g, 38%) as a white solid: LC/MS (Table 1, Method a) Rt=1.70 min; MS m/z: 375 (M+H)+.

Provenance & Evidence