Reaktion #167692

Reaktionsgleichung

HCl

sodium nitrite

solution

9-amino-3-benzyl-2,3,4,4a,5,6-hexahydrobenzo[f]pyrazino[1,2-a][1,4]diazepin-7(1H)-one

→

title compound

3-benzyl-2,3,4,4a,5,6-hexahydropyrazino[1,2-a][1,4]benzodiazepin-7(1H)-one

Lösungsmittel

water

hypophosphorous acid

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigequenched with 1M NaOH(aqueous)
2. 2
   Sonstigeto reach room temperature
3. 3
   workup.ADDITIONwas poured into 100 mL 1M NaOH(aqueous)
4. 4
   workup.ADDITIONAdditional 1M NaOH(aqueous) was added until the pH=14
5. 5
   ExtraktionThe product was extracted with dichloromethane three times
6. 6
   Trocknendried over sodium sulfate
7. 7
   Sonstigethe solvent was evaporated
8. 8
   SonstigeThe residue was then purified by reverse phase HPLC

Vorschrift

A solution of sodium nitrite (0.033 g, 0.478 mmol) in water (2.171 mL) was added to an ice bath chilled solution of Example 45H (0.14 g, 0.434 mmol) in hypophosphorous acid, solution in water (9.03 mL, 87 mmol, 9.63M) and HCl (2.140 mL, 26.1 mmol, 12.2M). A sample was taken out after 10 minutes, quenched with 1M NaOH(aqueous), and the reaction was determined to be complete by LC/MS. The reaction mixture was allowed to reach room temperature and was poured into 100 mL 1M NaOH(aqueous). Additional 1M NaOH(aqueous) was added until the pH=14. The product was extracted with dichloromethane three times, dried over sodium sulfate, and the solvent was evaporated. The residue was then purified by reverse phase HPLC to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.03 (s, 1H), 8.19 (t, J=5.8, 1H), 7.61-7.50 (m, 5H), 7.50-7.39 (m, 2H), 7.11 (t, J=7.3, 1H), 7.04 (d, J=7.9, 1H), 4.47 (s, 2H), 3.37-3.10 (m, 6H), 3.02 (dd, J=6.5, 14.9, 1H); MS (ESI+) m/z 308.0 (M+H)+.

Quelle