Piperidine → HCID 178430018, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing [(1-(4-fluorophenyl)prop-1-enyl]pyrrolidine (freshly prepared before use from 4′-fluoropropio phenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.65 g, 8.04 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.70 g, 8.04 mmol), N,N-diisopropylethylamine (1.4 mL, 8.04 mmol), piperidine (1.3 mL, 12.9 mmol), NEt3 (1.4 mL) and SnCl2 (24 mL of a 2 M soln in DMF). In this example the SnCl2 solution was added to the reaction mixture at 140° C. The mixture was stirred at 140° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The residue was purified by flash chromatography on silica gel with 95:5 CHCL3/MeOH as eluant to give 608 mg (23%) of 6-(4-fluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored gummy solid. This compound (601 mg, 1.85 mmol) was dissolved in 5:1 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 mmol). The solution was allowed 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 285 mg (10%) of the title compound as a beige colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.68 (br s, 6), 2.32 (s, 3), 2.63 (s, 3), 4.04 (br t, 4, J=5.1), 7.43 (t, 2, J=8.7), 7.72 (dd, 2, J=7.8, 8.1), 11.93 (s, 1), 14.10 (s, 1). MS m/z: 325 (M+1 for free base). Anal. Calcd for C19H21FN4.HCl.0.3H2O: C, 62.30; H, 6.22; N, 15.30; Cl, 9.68. Found: C, 62.14; H, 6.11; N, 15.24; Cl, 9.66.

Provenance & Evidence