反应详情

To a flask containing 3-methyl-6-[2-(piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one hydrochloride (123 mg, 0.40 mmol) was added in 2 mL of EtOH and NaOH (79 μl, 0.40 mmol). The solvent was removed and the free amine redissolved in DCM and filtered directly into a flask containing 2-methoxy-4-(2-oxoethyl)benzonitrile (58 mg, 0.33 mmol). The mixture was allowed to stir for 20 minutes before sodium triacetoxyborohydride (210 mg, 0.99 mmol) was added. The reaction stirred for 1 hour before being quenched with MeOH. The crude reaction was stirred an additional 30 minutes and the excess solvent was removed. The crude material was redissolved in DCM, filtered, concentrated and purified via MPLC [10-50% (10% MeOH in DCM)/DCM)] to afford 90 mg (63% yield) of 2-methoxy-4-(2-{4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazin-1-yl}ethyl)benzonitrile. 1H NMR (500 MHz; DMSO): 7.80 (d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.27 (d, J=7.8 Hz, 1H), 7.22 (s, 1H), 7.14 (s, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.65 (m, 1H), 3.88 (bs, 4H), 2.94 (m, 4H), 2.78 (m, 4H), 2.43 (m, 4H), 1.38 (d, J=6.8 Hz, 3H). LC-MS (IE, m/z): 375 [M+1]+. (0.098 μM)

1. customThe solvent was removed
2. dissolutionthe free amine redissolved in DCM
3. filtrationfiltered directly into a flask
4. additionwas added
5. custombefore being quenched with MeOH
6. customThe crude reaction
7. stirringwas stirred an additional 30 minutes
8. customthe excess solvent was removed
9. dissolutionThe crude material was redissolved in DCM
10. filtrationfiltered
11. concentrationconcentrated
12. custompurified via MPLC [10-50% (10% MeOH in DCM)/DCM)]