Piperidine → HCID 178423284, compound

Participants

Reaction Steps

Using the method described in Example 30 by employing [1-[4-(trifluoromethyl)phenyl]vinyl]pyrrolidine (freshly prepared before use from 4-(trifluoromethyl) acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.21 g, 5.02 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.00 g, 5.02 mmol), N,N-diisopropylethylamine (0.9 mL, 5.02 mmol), piperidine (0.8 mL, 8.0 mmol), NEt3 (1.0 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 248 mg (14%) of 2-methyl-4-piperidyl-6-[4-(trifluoromethyl)phenyl]pyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (245 mg, 0.69 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.70 mL, 0.70 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 187 mg (10%) of the title compound as a beige colored solid. Mp: 278-280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.72 (br s, 6), 2.58 (s, 3), 4.08 (s, 4), 7.05 (s, 1), 7.93 (d, 2, J=8.3), 8.20 (d, 2, J=8.2), 12.16 (s, 1), 14.32 (s, 1). MS m/z: 361 (M+1 for free base). Anal. Calcd for C19H19F3N4.HCl.1.5H2O: C, 53.79; H, 5.43; N, 13.21; Cl, 8.26. Found: C, 54.01; H, 5.40; N, 13.18; Cl, 8.60.

Provenance & Evidence