反应详情

温度

140 °C

Using the method described in Example 30 by employing (1-phenylbut-1-enyl)pyrrolidine (freshly prepared before use from butyrophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.63 g, 8.11 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.60 g, 8.11 mmol), N,N-diisopropylethylamine (1.4 mL, 8.11 mmol), piperidine (1.3 mL, 13.0 mmol), NEt3 (1.3 mL) and SnCl2 (24 mL of a 2 M soln in DMF). In this example the SnCl2 solution was added to the reaction mixture at 140° C. The mixture was stirred at 140° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The residue was purified by flash chromatography on silica gel with 100% EtOAc as eluant to give 0.42 g (16%) of 7-ethyl-2-methyl-6-phenyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (411 mg, 1.31 mmol) was dissolved in 5:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.30 mL, 1.30 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 34 mg (1%) of the title compound as a white colored solid. Mp: 261-263° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.05 (t, 3, J=7.5), 1.63 (br s, 6), 2.56 (s, 3), 2.69 (q, 2, J=7.2), 3.95 (br s, 4), 7.46-8.02 (m, 5), 11.90 (s, 1), 13.86 (s, 1). MS m/z: 321 (M+1 for free base). Anal. Calcd for C20H24N4.HCl.0.7H2O: C, 65.01; H, 7.20; N, 15.17; Cl, 9.59. Found: C, 65.09; H, 6.90; N, 14.98; Cl, 9.85.

1. customwas added to the reaction mixture at 140° C
2. temperatureto cool to room temperature
3. customThe residue was purified by flash chromatography on silica gel with 100% EtOAc as eluant