反应详情

温度

50 °C

A mixture of 3-bromo-2-oxo-cyclohexanecarboxylic acid diethylamide (35; prepared according to Example 7(c)) (336 mg, 1.2 mmol) and (2-fluoro-ethyl)-(4-fluoro-phenyl)-amine (38) (383 mg, 2.4 mmol) was stirred under N2 at 50° C. for 3 h and the reaction turned brown. The resulting mixture was dissolved in propan-2-ol (2 mL) and dry zinc chloride (491 mg, 3.6 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (20 mL) and washed with 2 N HCl (10 mL), water (2×10 mL) and aqueous potassium carbonate solution (2×5 mL) then dried and concentrated in vacuo. The crude material was triturated with diethyl ether to afford 40 mg (10%) of 6-fluoro-9-(2-fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (non-radioactive imaging agent 9) as white solid. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δH 1.13 (3H, t, J=9 Hz, N(CH2CH3)2), 1.30 (3H, t, J=9 Hz, N(CH2CH3)2), 1.55-2.14 (4H, m, 2- and 3-CH2), 2.78-2.86 (2H, m, 1-CH2), 3.36-3.67 (4H, m, N(CH2CH3)2), 4.00-4.10 (1H, m, 4-CH), 4.30 (2H, dm, J=21 Hz, NCH2CH2F), 4.60 (2H, dm, J=41 Hz, NCH2CH2F), 6.75-6.95 (2H, m, NCCHCHCFCH), and 7.05-7.15 (1H, m, NCCHCHCFCH.

1. temperatureThe mixture was heated
2. temperatureto reflux under N2 for 16 h
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
5. washwashed with 2 N HCl (10 mL), water (2×10 mL) and aqueous potassium carbonate solution (2×5 mL)
6. customthen dried
7. concentrationconcentrated in vacuo
8. customThe crude material was triturated with diethyl ether