Reaction Steps
To a stirred suspension of the step-2 intermediate (0.15 g, 0.52 mmol), K2CO3 (0.138 g, 1 mmol) and KI catalytic amount in 1 mL of DMSO was added a DMSO solution of intermediate 20 (0.98 g, 0.5 mmol) and the reaction mixture was stirred for 12 hours under nitrogen atmosphere. After completion of the reaction, it was diluted with ethyl acetate and water. The layers were separated and the aqueous layer was washed twice with ethyl acetate. The combined organic layers was dried over anhydrous Na2SO4, concentrated and purified by chromatography to yield (2S,4S)-4-fluoro-1-(2-((1S,3S)-3-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-1,2,2-trimethylcyclopentylamino)acetyl)pyrrolidine-2-carbonitrile. (2S,4S)-4-fluoro-1-(2-((1S,3S)-3-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-1,2,2-trimethylcyclopentylamino)acetyl)pyrrolidine-2-carbonitrile (0.032 g, 0.08 mmole) was dissolved in ethyl acetate and solution of methanesulphonic acid (7.9 mg, 0.08 mmole) in 1 mL ethyl acetate was added and stirred for one hour. Then ethyl acetate was concentrated and washed with diethyl ether to obtain the title compound. 0.03 g, Off white hygroscopic solid. 1H NMR (400 MHz, D2O) δ ppm: 1.02 (s, 3H), 1.09 (s, 3H), 1.35 (s, 3H), 1.37 (d, 6H), 1.49-1.57 (m, 1H), 1.84-1.89 (m, 2H), 2.04-2.08 (m, 1H), 2.35-2.38 (m, 1H), 2.40-2.75 (m, 3H), 2.80 (s, 3H), 2.9-2.94 (m, 1H), 3.26-3.29 (m, 1H), 3.77-3.80 (m, 1H), 3.90-3.95 (m, 1H), 4.01-4.15 (m, 1H), 4.20-4.35 (m, 1H), 5.10, d, J=9.36 Hz, 0.8H), 5.25 (d, J=9.36 Hz, 0.2H), 5.55 (d, J=51 Hz, 0.2H), 5.56 (d, J=51 Hz, 0.8H). m/z (M+H): 406.2.
