Trifluoroacetic acid → 5-(2-Ethylsulfonyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

Participants

Reaction Conditions

Reaction Steps

2-ethylsulfonyl-3,3a,4,5,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole (36.34 mg, 0.1779 mmol) and Et3N (54.01 mg, 74.39 μL, 0.5337 mmol) were added to a solution of tert-butyl N-tert butoxycarbonyl-5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-ylcarbamate (100 mg, 0.1779 mmol) in DMF (2 mL) and the resulting solution heated at 100° C. for 2 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and washed successively with water (2×5 mL) followed by brine (1×5 mL). The organic layer was concentrated in vacuo to leave a solid. The solid was dissolved in CH2Cl2 (10 mL) and trifluoroacetic acid (405.7 mg, 274.1 μL, 3.558 mmol) was added. The reaction mixture was stirred at room temperature for 1 h and the reaction mixture then concentrated in vacuo to an oil. The oil was redissolved in CH2Cl2 (20 ml) and concentrated in vacuo to leave a solid. The solid was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, and freeze-dried to give the product (34.4 mg, 40% yield); 1H NMR (400 MHz, DMSO) d 1.25 (t, 3H), 3.1-3.2 (m, 4H), 3.25-3.3 (m, 2H), 3.4-3.45 (m, 2H), 3.5-3.7 (m, 4H), 6.75 (s, 2H), 7.6-7.65 (m, 3H) and 8.05-8.1 (m, 2H) ppm; MS (ES+) 442.1

Provenance & Evidence