反应详情

To a solution of the intermediate from step F (118 mg, 0.33 mmol) in DMF was added the ethyl 4-[(1S)-1-hydrazinoethyl]benzoate hydrochloride (89 mg, 0.36 mmol) and triethyl amine (55 μL, 0.39 mmol). After stirring the reaction mixture at room temperature for 18 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 25% ethyl acetate-hexanes. This material was then re-purified with 3% acetonitrile-dichloromethane to give the desired compound. 1H NMR (500 MHz, CDCl3): 8.76 (d, J=2.0 Hz, 1H), 8.04 (d, J=8.2 Hz, 2H), 7.92 (1.8 Hz, 1H), 7.85 (d, J=1.8 Hz, 2H), 7.68 (d, J=8.9 Hz, 1H), 7.5 (d, J=2.1 Hz, 1H), 7.36 (t, J=1.8 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 6.76 (s, 1H), 4.42 (q, J=7.0 Hz, 1H), 4.03 (s, 3H), 2.04 (s, 3H), 2.01 (t, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). LC-MS: 4.28 min; (M+H)=546.0.

1. concentrationwas 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 3% acetonitrile-dichloromethane