Piperidine → HCID 178423281, compound

Participants

Reaction Steps

Using the method described in Example 30 by employing [1-(2-(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 2-(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.19 g, 4.94 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 4.94 mmol), N,N-diisopropylethylamine (0.9 mL, 4.94 mmol), piperidine (0.8 mL, 7.9 mmol), NEt3 (0.9 mL) and SnCl2 (15 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 330 mg (19%) of 2-methyl-4-piperidyl-6-[2-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a tan colored solid. This material (330 mg, 0.90 mmol) was dissolved in 5:1 EtOAc/MeOH (40 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 202 mg (11%) of the title compound as beige colored cube shaped crystals. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.70 (br s, 6), 2.58 (s, 3), 4.01 (s, 4), 6.62 (s, 1), 7.74 (d, 1, J=7.5), 7.79 (t, 1, J=7.5), 7.86 (t, 1, J=7.4), 7.97 (d, 1, J=7.8), 12.45 (s, 1), 14.43 (s, 1). MS m/z: 361 (H+1 for free base). Anal. Calcd for C19H19F3N4.HCl.H2O: C, 55.00; H, 5.35; N, 13.51; Cl, 8.55. Found: C, 55.25; H, 5.41; N, 13.31; Cl, 8.76.

Provenance & Evidence