Piperidine → HCID 178487381, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 1,2,3-trimethoxy-5-(1-pyrrolidinylvinyl) benzene (freshly prepared before use from 3,4,5-trimethoxyacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.70 g, 6.46 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.35 g, 6.46 mmol), N,N-diisopropylethylamine (1.1 mL, 6.46 mmol), piperidine (1.0 mL, 10.3 mmol), NEt3 (1.1 mL) and SnCl2 (19 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 0.85 g (35%) of 1,2,3-trimethoxy-5-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene as a beige colored solid. This compound (466 mg, 1.20 mmol) was dissolved in 1:3 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.20 mL, 1.20 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 409 mg (29%) of the title compound as white colored crystals. Mp: 275-277° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.52 (s, 3), 3.66 (s, 3), 3.39 (s, 6), 3.99 (br t, 4, J=5.2), 6.85 (s, 1), 7.75 (s, 2), 11.94 (s, 1), 14.28 (s, 1). MS m/z: 381 (M+1 for free base). Anal. Calcd for C21H26N4O3.HCl: C, 60.21; H, 6.50; N, 13.37; Cl, 8.46. Found: C, 60.24; H, 6.53; N, 13.37; Cl, 8.57.

Provenance & Evidence