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0 °C

A solution of diisopropylamine (559 μL, 3.99 mmol) in dry tetrahydrofuran (1.2 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (1.6 mL, 3.99 mmol). The resulting reaction mixture was allowed to warm to 0° C. and then was treated with 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-propionamide (463.1 mg, 1.22 mmol) in small portions. The reaction mixture turned orange in color. The reaction mixture was then allowed to warm to 25° C. where it was stirred for 30 min. After 30 min at 25° C., the reaction mixture was cooled back down to 0° C. and then treated with a 1M solution of tributylborane in tetrahydrofuran (1.8 mL, 1.84 mmol). The resulting reaction mixture was stirred at 0° C. for 10 min then allowed to warm to 25° C. The reaction mixture was stirred at 25° C. for 30 min then heated under reflux for 20 h. The reaction mixture was cooled to 0° C. and then treated with water (3 mL) followed by sodium acetate (702.5 mg, 8.56 mmol) and then finally hydroxyamine-O-sulfonic acid (484.2 mg, 4.28 mmol). The resulting reaction mixture was stirred at 0° C. for 30 min then allowed to warm to 25° C. where it was stirred for 44 h. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The resulting aqueous residue was diluted with ethyl acetate (150 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/2 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-sulfamoyl-phenyl)-N-thiazol-2-yl-propionamide (191.8 mg, 72%) as a white solid: mp 179-181° C.; EI-HRMS m/e calcd for C17H21N3O2S2 (M+) 379.1024, found 379.1029.

1. customThe resulting reaction mixture
2. temperatureto warm to 25° C. where it
3. waitAfter 30 min at 25° C.
4. temperaturethe reaction mixture was cooled back down to 0° C.
5. customThe resulting reaction mixture
6. stirringwas stirred at 0° C. for 10 min
7. temperatureto warm to 25° C
8. stirringThe reaction mixture was stirred at 25° C. for 30 min
9. temperaturethen heated
10. temperatureunder reflux for 20 h
11. temperatureThe reaction mixture was cooled to 0° C.
12. customThe resulting reaction mixture
13. stirringwas stirred at 0° C. for 30 min
14. temperatureto warm to 25° C. where it
15. stirringwas stirred for 44 h
16. concentrationThe reaction mixture was concentrated in vacuo
17. customto remove tetrahydrofuran
18. additionThe resulting aqueous residue was diluted with ethyl acetate (150 mL)
19. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×100 mL)
20. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate
21. filtrationfiltered
22. concentrationconcentrated in vacuo