Ethyl Acetate → HCID 135936828, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (8.00 g, 13.8 mmol), 1,4-dioxane (80 mL) and 1 N aqueous NaOH (30.0 mL, 30.0 mmol) was heated at about 60° C. for about 2 h. Then the reaction was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/Et2NH (970:27:3) in DCM followed by DCM/MeOH/Et2NH (950:45:5). The product-containing fractions were combined, concentrated under reduced pressure, and dried in a vacuum oven at about 70° C. for about 12 h to give a solid. The solid was triturated with Et2O, filtered while washing with additional Et2O, and dissolved in hot MeOH. The solution was concentrated under reduced pressure to give a solid. The solid was dissolved in hot MeOH (˜200 mL), sonicated while cooling until a suspension formed, concentrated under reduced pressure, and dried in a vacuum oven at about 50° C. to give an off-white solid. To the solid was added EtOAc (30 mL) to give a suspension which was heated briefly with a heat gun and then sonicated for about 15 min. After sitting at ambient temperature for about 15 min, the resulting white solid was collected by vacuum filtration, washing with additional EtOAc (15 mL), and dried in a vacuum oven at about 50° C. The solid was dissolved in hot EtOH (˜200 mL), filtered to remove minor insolubles (<10 mg), sonicated for about 10 min, while cooling, to give a white suspension, which was concentrated under reduced pressure. The resulting white solid was dried in a vacuum oven at about 60° C. to give N-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (3.43 g, 67%): LC/MS (Table 2, Method a) Rt=1.67 min; MS m/z: 375 (M+H)+.

Provenance & Evidence