Piperidine → HCID 178489270, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 2-methoxy-1-(1-pyrrolidinylvinyl)furan (freshly prepared before use from 2′-methoxy acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.14 g, 10.5 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.25 g, 10.5 mmol), N,N-diisopropylethylamine (1.8 mL, 10.5 mmol), piperidine (1.7 mL, 16.8 mmol), NEt3 (1.8 mL) and SnCl2 (32 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 2.49 g (74%) of 2-methoxy-1-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene as a beige colored foam. This compound (864 mg, 2.67 mmol) was dissolved in 10:1 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (2.70 mL, 2.70 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 654 mg (50%) of the title compound as a pale yellow colored solid. Mp: 261-263° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.64 (br s, 6), 2.51 (s, 3), 3.83 (s, 3), 3.97 (br s, 4), 6.72 (s, 1), 7.07 (dt, 1, J=0.7, 7.4), 7.18 (d, 1, J=8.2), 7.44 (dt, 1, J=1.7, 7.1), 7.67 (dd, 1, J=1.3, 7.6), 11.74 (s, 1), 14.31 (s, 1). MS m/z: 411 (M+1 for free base). Anal. Calcd for C19H22N4O.HCl.H2O: C, 60.55; H, 6.69; N, 14.87; Cl, 9.41. Found: C, 60.68; H, 6.78; N, 14.82; Cl, 9.52.

Provenance & Evidence