反应详情

Combine 4-(5-Oxo-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-benzamide (Intermediate 26, 120.0 mg, 0.43 mmol), Benzylamine (70 uL, 0.64 mmol), THF (3 mL), and Ti(OiPr)4 (0.2 mL, 0.68 mmol) at 0° C. Stir the reaction for 12 hours allowing it to come to room temperature and then add TiCl4 (0.7 mL, 0.68 mmol) at 0° C. After reaction stirs for 3 hours, add BH3SMe2 at room temperature. After the reaction stirs for 72 hours, add 1N NaOH aq (6 mL) at room temperature. Upon addition, a precipitate forms. Allow the reaction to stir for an additions 12 hours, centrifuge, and decant off aqueous and organic layers. Separate the organic layer and concentrate. Add the organic mixture to a 2 g SCX column, wash with MeOH, and elute with 1N NH3 MeOH. Purify using reverse phase chromatography (5% to 95% 0.001% TFA buffer in acetonitrile/water) to afford 19.4 mg, 0.05 mmol (12% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 1.7-1.8 (2H, m), 1.9-2.1 (3H, m), 2.6-2.9 (2H, m), 3.8-4.0 (3H, m), 6.7-6.9 (2H, m), 6.9-7.0 (2H, m), 7.2-7.5 (6H, m), 7.7-7.9 (2H,m); MS m/z 284 (M of SM+3).

1. customat 0° C
2. customthe reaction for 12 hours
3. customto come to room temperature
4. customat 0° C
5. customAfter reaction stirs for 3 hours
6. additionadd BH3SMe2 at room temperature
7. additionUpon addition
8. customAllow the reaction
9. stirringto stir for an additions 12 hours, centrifuge
10. customdecant off aqueous
11. customSeparate the organic layer
12. concentrationconcentrate
13. additionAdd the organic mixture to a 2 g SCX column
14. washwash with MeOH
15. washelute with 1N NH3 MeOH
16. customPurify