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2-[5-Ethynyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.002 g, 2.56 mmol) was dissolved in dioxane (5 mL) and 4 M HCl in dioxane (5 mL) was added. The reaction mixture was stirred for 3 hours and concentrated. To the residue was added 2-Methoxycarbonylamino-3-methyl-butyric acid (561 mg, 3.20 mmol), HATU (1.22 g, 3.20 mmol) and DMF (15 mL). The stirred reaction mixture was cooled to 0° C. and DIPEA (2.23 mL, 12.8 mmol) was added). After stirring for 3 h, the reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate and brine. The combined organic layers were dried over magnesium sulfate and concentrated. The crude residue was purified by silica column chromatography (40% to 75% EtOAc/hexanes) to provide the coupled compound (741 mg, 65% over 2 steps). This material was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (5 mL) was added. The stirred reaction mixture was heated to reflux for 4 h, then cooled to RT, and poured into a saturated aqueous solution of sodium bicarbonate. The aqueous phase was extracted 3 times with dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated. The crude residue was purified by silica column chromatography (0% to 10% MeOH/DMC) to provide {1-[2-(5-Ethynyl-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (525 mg, 100%).

1. concentrationconcentrated
2. customThe stirred reaction mixture
3. stirringAfter stirring for 3 h
4. washwashed with a saturated aqueous solution of sodium bicarbonate and brine
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. concentrationconcentrated
7. customThe crude residue was purified by silica column chromatography (40% to 75% EtOAc/hexanes)
8. customto provide the coupled compound (741 mg, 65% over 2 steps)
9. customThe stirred reaction mixture
10. temperaturewas heated
11. temperatureto reflux for 4 h
12. temperaturecooled to RT
13. extractionThe aqueous phase was extracted 3 times with dichloromethane
14. dry with materialThe combined organic layers were dried over magnesium sulfate
15. concentrationconcentrated
16. customThe crude residue was purified by silica column chromatography (0% to 10% MeOH/DMC)