Piperidine → HCID 178489869, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 1-methoxy-3-(1-pyrrolidinylvinyl)benzene (freshly prepared before use from 3-methoxyacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.49 g, 12.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.52 g, 12.3 mmol), N,N-diisopropylethylamine (2.1 mL, 12.3 mmol), piperidine (1.9 mL, 19.7 mmol), NEt3 (2.0 mL) and SnCl2 (37 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 1.35 g (34%) of 1-[2,7-dimethyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]-3-methoxybenzene as a beige colored solid. This compound (463 mg, 1.43 mmol) was dissolved in 5:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 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 485 mg (32%) of the title compound as a white colored solid. Mp: 241-243° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.50 (s, 3), 3.79 (s, 3), 3.98 (br s, 4), 6.84 (s, 1), 7.03 (dd, 1, J=1.0, 8.3), 7.38 (t, 1, J=3.9), 7.44-7.46 (m, 2), 11.91 (s, 1), 14.36 (s, 1). MS m/z: 323 (M+1 for free base). Anal. Calcd for C19H22N4O.HCl.0.5H2O: C, 62.03; H, 6.58; N, 15.23; Cl, 9.64. Found: C, 62.08; H, 6.56; N, 15.17; Cl, 9.75.

Provenance & Evidence