反应详情

Partition 4-chloromethyl-thiazole hydrochloride (199 mg, 1.17 mmol) between Et2O (20 mL) and saturated aqueous NaHCO3 (20 mL). Separate the layers and dry the ether layer over MgSO4. Add DMF (3 mL) to the ether layer and concentrate in vacuo to remove the ether. Add this solution to a slurry of N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (Preparation 3) (300 mg, 1.07 mmol) and sodium hydride (60% suspension in mineral oil, 47 mg, 1.17 mmol) in DMF (3 mL) which has stirred for 30 min at room temperature. Stir the reaction at room temperature for 2 h, then add aqueous NaHCO3 (30 mL) and EtOAc (50 mL). Separate the layers and wash the organic portion with aqueous NaHCO3 (2×30 mL). Dry the organic layer (MgSO4). Filter and concentrate in vacuo to obtain 487 mg crude yellow solid. Recrystallize the material from boiling toluene (10 mL) to afford 296 mg (73%) of the title compound as a yellow solid. MS (ES): m/z 379 (M+1), 377 (M−1); 1H NMR (DMSO-d6): δ 9.01 (d, 1H, J=1.8 Hz), 7.90 (d, 1H, J=1.3 Hz), 7.84 (d, 1H, J=7.9 Hz), 7.69 (d, 1H, J=8.4 Hz), 7.56 (d, 1H, J=1.8 Hz), 7.40 (dd, 1H, J=8.6, 1.5 Hz), 5.47 (s, 2H), 3.99 (m, 1H), 3.03-2.81 (m, 3H), 2.49 (m, 1H), 2.37 (m, 1H), 1.98 (m, 1H), 1.80 (m, 1H), 0.99 (d, 6H, J=7.0 Hz); HPLC (Method A): Rt=1.93 min, (97%).

1. customSeparate the layers
2. dry with materialdry the ether layer over MgSO4
3. concentrationAdd DMF (3 mL) to the ether layer and concentrate in vacuo
4. customto remove the ether
5. stirringStir
6. customthe reaction at room temperature for 2 h
7. customSeparate the layers
8. washwash the organic portion with aqueous NaHCO3 (2×30 mL)
9. dry with materialDry the organic layer (MgSO4)
10. filtrationFilter
11. concentrationconcentrate in vacuo
12. customto obtain 487 mg crude yellow solid
13. customRecrystallize the material