Piperidine → HCID 178423283, compound

Participants

Reaction Steps

Using the method described in Example 30 by employing [1-(3-(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 3-(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.97 g, 8.17 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.70 g, 8.17 mmol), N,N-diisopropylethylamine (1.4 mL, 8.17 mmol), piperidine (1.3 mL, 13.1 mmol), NEt3 (1.3 mL) and SnCl2 (25 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 500 mg (17%) of 2-methyl-4-piperidyl-6-[3-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (500 mg, 1.39 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.40 mL, 1.40 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 493 mg (15%) of the title compound as a white colored solid. Mp: 241-243° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.72 (br s, 6), 2.59 (s, 3), 4.08 (s, 4), 7.14 (s, 1), 7.79 (t, 1, J=7.6), 7.85 (d, 1, J=7.5), 8.30 (d, 1, J=7.6), 8.34 (s, 1), 12.92 (s, 1), 14.53 (s, 1). MS m/z: 361 (M+1 for free base). Anal. Calcd for C19H19F3N4.HCl.1.0H2O: C, 55.00; H, 5.35; N, 13.51; Cl, 8.55. Found: C, 54.99; H, 5.20; N, 13.39; Cl, 8.60.

Provenance & Evidence