反应详情

Using the method described in Example 30 by employing [1-(2,5-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 2′,5′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.45 g, 6.94 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 4.83 mmol), N,N-diisopropylethylamine (1.2 mL, 6.94 mmol), piperidine (1.1 mL, 11.1 mmol), NEt3 (1.2 mL) and SnCl2 (21 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 417 mg (26%) of 6-(2,5-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a tan colored foam. This material (415 mg, 1.25 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.30 mL, 1.30 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 337 mg (19%) of the title compound as white colored needles. Mp: 279-281° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.06 (s, 4), 6.85 (s, 1), 7.42-7.55 (m, 2), 7.86-7.91 (m, 1), 12.13 (s, 1), 14.41 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.0H2O: C, 56.54; H, 5.50; N, 14.65. Found: C, 56.29; H, 5.61; N, 14.53.

1. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant