反应详情

1-[(2,2-Difluorocyclopropyl)methyl]-5-(1,2,3,3a,4,6a-hexahydrocyclo-penta-[c]pyrrol-5-yl)-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (24-2, 0.79 g, 2.1 mmol, 1.0 equiv), (2S)-3,3,3-trifluoro-2-hydroxypropanoic acid (24-3, 0.30 g, 2.1 mmol, 1.0 equiv), EDC (0.40 g, 2.1 mmol, 1.0 equiv), HOBT (0.32 g, 2.1 mmol, 1.0 equiv) and triethylamine (0.58 mL, 4.2 mmol, 2.0 equiv) were added to anhydrous DMF (13.6 mL) and stirred at RT. After 18 h, the contents were partitioned between ethyl acetate (50 mL) and saturated NaHCO3 (20 mL). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (2×20 mL). The combined organics were washed with H2O (5×20 mL), dried over Na2SO4, filtered and concentrated in vacuo to give a dark red oil. Purification by normal-phase chromatography (0-60% EtOAc:Hex) afforded 24-4 as a white solid. MS m/z (M+H): calculated=509.1276; observed=509.1281.

1. customthe contents were partitioned between ethyl acetate (50 mL) and saturated NaHCO3 (20 mL)
2. customThe layers were separated
3. extractionthe aqueous layer was back-extracted with ethyl acetate (2×20 mL)
4. washThe combined organics were washed with H2O (5×20 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give a dark red oil
9. customPurification by normal-phase chromatography (0-60% EtOAc:Hex)