反应详情

4-[4-(3-piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile (265 mg, 0.81 mmol), DCM (10.6 ml), HOBT (120 mg, 0.89 mmol), FMoc (L)-aniline (277 mg, 0.89 mmol) and EDCl.HCl (171 mg, 0.89 mmol) were stirred at ambient temperature overnight. Water (10 ml) was added and stirred for one hour, the mixture was filtered and the organic phase separated and washed with water (10 ml), the organic phase was dried over MgSO4, filtered and concentrated in vacuo at 35° C. The residue was dissolved in DCM (9 ml) and piperidine (86 mg, 10 mmol) was added, the mixture was stirred at ambient temperature for one hour. To the reaction mixture, water (5 ml) was added and the organic phase separated, dried over MgSO4, filtered and concentrated in vacuo at 35° C. The crude material was subjected to chromatography on silica eluting with 2% MeOH in DCM to provide title compound (136 mg, 42%). 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.77 (q, 1H), 3.65 (br s, 2H), 3.49 (br s, 2H), 2.55 (t, 2H), 2.45 (br s, 4H), 2.14-2.00 (m, 4H), 1.97 (m, 2H), 1.58 (br s, 2H), 1.25 (d, 3H).

1. filtrationthe mixture was filtered
2. customthe organic phase separated
3. washwashed with water (10 ml)
4. dry with materialthe organic phase was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo at 35° C
7. dissolutionThe residue was dissolved in DCM (9 ml)
8. stirringthe mixture was stirred at ambient temperature for one hour
9. customthe organic phase separated
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo at 35° C