反应详情

To a solution of the intermediate from step C (152 mg, 0.46 mmol) in DMF (5 mL) was added the ethyl 4-[(1S)-1-hydrazinoethyl]benzoate hydrochloride (126 mg, 0.51 mmol) and triethyl amine (86 μL, 0.61 mmol). After stirring, the reaction mixture at room temperature for 2 hours it was concentrated in vacuo. The residue was diluted with water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using 10% ethyl acetate-hexanes. This material was then re-purified with 75% hexanes-dichloromethane to give the desired compound as the major product. 1H NMR (CDCl3, 500 MHz): 8.84 (d, J=2.0 Hz, 1H), 8.18 (d, J=8.5 Hz, 1H), 8.03 (d, J=8.2 Hz, 2H), 7.99 (d, J=2.1 Hz, 1H), 7.83 (d, J=1.8 Hz, 2H), 7.78 (m, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.34 (t, J=1.8 Hz, 1H), 7.28 (d, J=8.2 Hz, 2H), 6.77 (s, 1H), 5.58 (q, J=7.1 Hz, 1H), 4.41 (q, J=7.1 Hz, 2H), 2.02 (d, J=7.1 Hz, 3H), 1.4 (t, J=7.0 Hz, 3H). LC-MS: 4.64 min; (M+H)=516.3.

1. concentrationthe reaction mixture at room temperature for 2 hours it was concentrated in vacuo
2. additionThe residue was diluted with water and ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography
8. customThis material was then re-purified with 75% hexanes-dichloromethane