Nitrogen → HCID 178477934, compound

Participants

Reaction Steps

To a mixture of 1-(N-pyrrolyl)-1-phenyl ethylene (1.54 g, 8.90 mmol) [freshly prepared through TiCl4 mediated condensation between acetophenone (Aldrich Chemical Company) and pyrrolidine (Aldrich Chemical Company) (1.70 g, 8.76 mmol) in ether by the method described by Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782-5789)] and N, N-diisopropylethylamine (1.60 mL, 9.10 mmol) in toluene (15 mL) at room temperature was added 4,6-dichloro-5-nitro pyrimidine (Aldrich Chemical Company) (1.70 g, 8.76 mmol) slowly under a stream of N2. The reaction mixture became hot upon mixing and was stirred at room temperature for 2.5 h. The solution was filtered through a fritted-funnel and the residue was washed with hot toluene (3×). The filtrate was concentrated in vacuo and the residue was dissolved in 1:2 toluene:dioxane (8.0-16.0 mL). Piperidine (Aldrich Chemical Company) (2.0 mL, 20 mmol) and Et3N (2.0 mL) were slowly added (exothermic reaction). The mixture was stirred at 100° C. (sand bath temperature) for 1 h and cooled under a N2 stream. To this solution was added SnCl2 (32 mL of a 1.5 M solution in DMF) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into a mixture of NaOH (3.80 g, 95.0 mmol) and ice (˜100 mL) and stirred vigorously for 30 min. The resulting slurry (pH ˜9) was filtered through a pad of celite, and the residue was washed exhaustively with 10:1 EtOAc:MeOH. The clear filtrate was separated and the organic phase was washed with H2O (4×), saturated aqueous NaCl, dried over Na2SO4, filtered, and concentrated with a rotary evaporator. The residue was purified by flash chromatography on silica gel with a gradient eluant of 0.4:99.6 i-PrOH:CH2Cl2 to 5:95 i-PrOH:CH2Cl2 to afford 0.73 g (30%) of the title compound as a brown solid. A portion of this material was converted to it's corresponding HCl salt by treating a solution of the free base in CH2Cl2 with 1N ethereal HCl. The resulting solid was filtered and washed with hot EtOAc. MS m/z+: 279 (M+1); m/z−: 277 (M−1). 1H NMR (CD3OD; 500 MHz): δ 2.12 (br s, 6), 4.53 (br s, 4), 8.01 (m, 2), 7.52 (s, 1), 7.85 (m, 3), 8.56 (s, 1). HRMS: Calcd for M+H, C17H19N4: 279.1606. Found: 279.1606

Provenance & Evidence