1-Azabicyclo[3.2.2]nonan-4-one → 7-bromo-9-fluoro-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole
반응식
Cl.[Br:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[NH:10]N.[N:12]12[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[C:15](=O)[CH2:14][CH2:13]2>Cl.C(O)(=O)C>[Br:2][C:3]1[C:4]2[NH:10][C:15]3[CH:16]4[CH2:19][CH2:20][N:12]([CH2:13][C:14]=3[C:5]=2[CH:6]=[C:7]([F:9])[CH:8]=1)[CH2:18][CH2:17]4참가 물질
4
반응 조건
- 온도
- 80 °C
실험 절차
(2-Bromo-4-fluorophenyl)hydrazine hydrochloride (1.14 g, 4.72 mmol; Enamine) was suspended in HCl-acetic acid (1.0 M, 25 mL; Aldrich). The product of Example 1A (684 mg, 4.91 mmol) was added and the reaction was heated to 80° C. for 5 hours. The reaction was then allowed to cool and then concentrated. The product was triturated with acetonitrile and isolated by filtration, washing with additional acetonitrile (2×10 mL). The solid was partitioned between 1.0 M NaOH (50 mL) and CHCl3 (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.05-2.11 (m, 4H), 3.01-3.14 (m, 3H), 3.19-3.26 (m, 2H), 4.17 (s, 2H), 6.96-7.04 (m, 2H); MS (DCI/NH3) m/z 309/311 (M+H)+. Anal. Calcd. for C14H14BrFN2: C, 54.39; H, 4.56; N, 9.06. Found: C, 54.04; H, 4.28; N, 8.90.