反应详情

To a mixture of 5-amino-1,3,4-thiadiazole-2-thiol (0.33 g, 2.5 mmol) in anhydrous DMF (8.5 mL) at room temperature add sodium hydride (0.1 g, 2.6 mmol, 60% dispersion in mineral oil) in portions. After stirring at room temperature for 10 min, add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.75 g, 2.3 mmol) in anhydrous DMF (5.6 mL). Stir at room temperature overnight and quench the reaction mixture with 10% aqueous NaHCO3 (25 mL). Extract the mixture with DCM (100 mL). Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (hexane over 10 min; 100:0 to 50:50 hexane/EtOAc over 23 min; 50:50 to 0:100 hexane/EtOAc over 33 min; 35 mL/min) to obtain an oil. Add EtOAc (16 mL) to precipitate product. After stirring overnight, filter the slurry, wash the solid with EtOAc (10 mL) and dry to obtain the desired intermediate (0.583 g, 61%) as a white solid. MS (ES+) m/z: 427.1 (M+H)+.

1. stirringStir at room temperature overnight
2. customquench the reaction mixture with 10% aqueous NaHCO3 (25 mL)
3. extractionExtract the mixture with DCM (100 mL)
4. dry with materialDry the organic phase over Na2SO4
5. filtrationfilter
6. concentrationconcentrate in vacuo
7. dissolutionDissolve the residue in DCM
8. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (hexane over 10 min; 100:0 to 50:50 hexane/EtOAc over 23 min; 50:50 to 0:100 hexane/EtOAc over 33 min; 35 mL/min)
9. customto obtain an oil
10. customAdd EtOAc (16 mL) to precipitate product
11. stirringAfter stirring overnight
12. filtrationfilter the slurry
13. washwash the solid with EtOAc (10 mL)
14. customdry