Piperidine → HCID 178423148, compound

Participants

Reaction Steps

Using the method described in Example 30 by employing [1-(3,5-bis(trifluoromethyl)phenyl)vinyl]pyrrolidine (freshly prepared before use from 3′,5′-bis(trifluoromethyl)acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.33 g, 4.30 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (0.90 g, 4.30 mmol), N,N-diisopropylethylamine (0.7 mL, 4.30 mmol), piperidine (0.7 mL, 6.90 mmol), NEt3 (1.0 mL) and SnCl2 (13 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica el with 95:5 CHCl3/MeOH as eluant to give 232 mg (13%) of 6-((3,5-bis(trifluoromethyl)phenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored oil. This material (232 mg, 0.54 mmol) was dissolved in 10:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.60 mL, 0.60 mmol). The solution was left to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 57 mg (3%) of the title compound as a beige colored solid. Mp: >280° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.73 (br s, 6), 2.60 (s, 3), 4.10 (s, 4), 7.30 (s, 1), 8.22 (s, 1), 8.68 (s, 2), 12.27 (s, 1), 14.43 (s, 1). MS m/z: 429 (M+1 for free base). Anal. Calcd for C20H18F6N4.HCl: C, 51.68; H, 4.12; N, 12.05; Cl, 7.63. Found: C, 51.51; H, 4.17; N, 11.96; Cl, 7.82.

Provenance & Evidence