Diisopropylethylamine → N-((1S,3R,4S)-3-ethyl-4-(5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)cyclopentyl)cyclopropanesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (0.158 g, 0.800 mmol) in DMF (8.7 mL) was added DIEA (0.419 mL, 2.399 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide•hydrochloride (0.215 g, 0.800 mmol). The reaction mixture was heated at about 60° C. for about 60 h. The temperature was increased to about 70° C. for about 2 h then DIEA (0.279 mL, 1.599 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide hydrochloride (0.093 g, 0.346 mmol) were added. The reaction mixture was heated at about 70° C. for about 2 h. Additional N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide hydrochloride (0.060 g, 0.223 mmol) was added and the reaction mixture was heated at about 70° C. for about 30 min. Additional DIEA (0.279 mL, 1.599 mmol) was added and the reaction mixture was heated at about 70° C. for about 1 h. The reaction mixture was cooled to ambient temperature and concd in vacuo. The residue was dissolved in EtOAc (25 mL) and washed with water (20 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give N-((1S,3R,4S)-3-ethyl-4-(5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)cyclopentyl)cyclopropanesulfonamide (0.134 g, 41%) as an orange solid: LC/MS (Table 1, Method n) Rt=0.66 min; MS m/z 394 (M+H)+.

Provenance & Evidence