反应详情

To a solution of 4-((1R,2R)-1-(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrile (intermediate 69d) (308 mg, 0.62 mmol) in CH2Cl2 (10 mL) and pyridine (1.5 mL) was added butyrylchloride (90 μL, 0.87 mmol) at room temperature. The resultant solution stirred for 90 hours and quenched with 2N aq. HCl (15 mL). The mixture was further partitioned between H2O (40 mL) and CH2Cl2 (35 mL). The aqueous layer was extracted with CH2Cl2 (35 mL). The combined organic extracts were washed with sat. aq. NaHCO3 (2×45 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a colourless oil (352 mg, 100%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.42 (s 1H), 7.93 (dm, J=8.8 Hz, 2H), 7.85 (dm, J=8.8 Hz, 2H), 7.51 (d, J=8.6 Hz, 1H), 6.94 (d, J=8.6 Hz, 1H), 5.74 (d, J=9.2 Hz, 1H), 5.03 (dd, J=6.5, 9.0 Hz, 1H), 4.66 (pentet, J=6.3 Hz, 1H), 2.38 (t, J=7.2 Hz, 2H), 2.35 (s, 3H), 1.70 (sextet, J=7.4 Hz, 2H), 1.44 (d, J=6.1 Hz, 3H), 0.95 (t, J=7.4 Hz, 3H), 0.81 (s, 9H), 0.09 (s, 3H), −0.01 (s, 3H).

1. customquenched with 2N aq. HCl (15 mL)
2. customThe mixture was further partitioned between H2O (40 mL) and CH2Cl2 (35 mL)
3. extractionThe aqueous layer was extracted with CH2Cl2 (35 mL)
4. washThe combined organic extracts were washed with sat. aq. NaHCO3 (2×45 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure