反应详情

To a slurry of EXAMPLE 208A (0.759 g, 2.02 mmol) in ethyl acetate (6 mL) and saturated sodium carbonate (6 mL) at 0° C., 2,2-dichloroacetic acid chloride was added neat in portions (15×40 μl 3 eq.). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then extracted with ethyl acetate (3×40 mL), washed with brine (40 mL), and dried over magnesium sulfate. The solvent was evaporated and 1.10 g of crude N-acetylated product was isolated as yellow oil (70% pure by HPLC). The crude 2,2-Dichloro-N-[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]-N-(2-hydroxyethyl)acetamide (1.00 g, 2.05 mmol) was dissolved in THF (27 mL) and water (27 mL). The solution was cooled to 0° C. and the pH was adjusted to 14-15 with aqueous KOH (50%). After 20 h, the reaction mixture was neutralized with aqueous HCl (1 M, 12 mL). The reaction mixture was extracted with ethyl acetate (3×25 mL), and the combined organic phases was dried over magnesium sulfate. Removal of solvent and purification by silica gel chromatography (gradient of 2-4% methanol in DCM) gave the title compound as a white solid (20 mg): HRMS calcd (found) for C16H18ClN3O5S2 m/z 431.0376 (431.0380).

1. customat 0° C.
2. extractionThe reaction mixture was then extracted with ethyl acetate (3×40 mL)
3. washwashed with brine (40 mL)
4. dry with materialdried over magnesium sulfate
5. customThe solvent was evaporated
6. custom1.10 g of crude N-acetylated product was isolated as yellow oil (70% pure by HPLC)
7. temperatureThe solution was cooled to 0° C.
8. waitAfter 20 h
9. extractionThe reaction mixture was extracted with ethyl acetate (3×25 mL)
10. dry with materialthe combined organic phases was dried over magnesium sulfate
11. customRemoval of solvent and purification by silica gel chromatography (gradient of 2-4% methanol in DCM)