反应详情

Using the method described in Example 30 by employing (1-fluoren-2-ylvinyl)pyrrolidine (freshly prepared before use from 2-acetylfluorene (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.27 g, 4.86 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.01 g, 4.86 mmol), N,N-diisopropylethylamine (0.9 mL, 4.86 mmol), piperidine (0.8 mL, 7.8 mmol), NEt3 (1.0 mL) and SnCl2 (15 mL of a 2 M soln in DMF). In this example the reaction mixture was stirred at room temperature for 48 h after the addition of 2 M SnCl2. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 325 mg (18%) of 6-fluoren-2-yl-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (321 mg, 0.86 mmol) was dissolved in 1:10 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.90 mL, 0.90 mmol). The solution was left 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 138 mg (7%) of the title compound as a beige colored solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.73 (br s, 6), 2.57 (s, 3), 4.05 (s, 2), 4.08 (br s, 4), 6.97 (s, 1), 7.39 (t, 1, J=7.2), 7.44 (t, 1, J=7.0), 7.66 (d, 1, J=7.2), 8.02 (d, 2, J=7.7), 8.10 (d, 1, J=8.0), 8.21 (s, 1), 12.01 (s, 1), 14.27 (s, 1). MS m/z: 381 (M+1 for free base). Anal. Calcd for C25H24N4.HCl.1.5H2O: C, 67.58; H, 6.31; N, 12.61; Cl, 7.88. Found: C, 67.77; H, 6.25; N, 12.54; Cl, 8.06.

1. customwas stirred at room temperature for 48 h
2. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant