Piperidine → HCID 178432641, compound

Participants

Reaction Steps

To a room temperature solution of [2-fluoro-1-phenylvinyl]pyrrolidine (freshly prepared before use from 2-fluoro-1-phenyl ethan-1-one (Example 152(a)), pyrrolidine and TiCl4 (see Example 30) (2.44 g, 12.7 mmol) in anhydrous toluene (15 mL) was added N,N-diisopropylethylamine (Aldrich Chemical Company) (2.0 mL, 12.7 mmol) followed by 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.61 g, 12.7 mmol). After stirring at room temperature for 2.5 h the reaction mixture was filtered through a fritted funnel. The residue was washed with hot toluene (2×30 mL) and the filtrate was concentrated under reduced pressure. The residue was dissolved with dioxane/toluene (20 mL:10 mL) and NEt3 (Aldrich Chemical Company) (2.1 mL) and piperidine (Aldrich Chemical Company) (2.0 mL, 20.3 mmol) were added. The mixture was stirred at 80° C. for 2 h under a N2 atmosphere. The SnCl2 solution was added to the reaction mixture at 80° C. The mixture was stirred at 80° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The reaction mixture was poured onto a mixture of NaOH (5 g) and crushed ice (150 mL) and stirred for 1 h. The resulting slurry was filtered through a Celite® pad, the pad was rinsed with 10:1 EtOAc/MeOH (4×60 mL). The filtrate was transferred to a seperatory funnel. The organic solution was separated, washed with H2O (3×350 mL), saturated NaCl (300 mL), dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with 50:50 EtOAc/hexanes as eluant to give 0.51 g (13%) of 7-fluoro-2-methyl-6-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored foam. This compound (0.51 g, 1.60 mmol) was dissolved in 10:1 EtOAc/MeOH (35 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.60 mL, 1.60 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 270 mg (6%) of the title compound as pale green colored needles. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.72 (br s, 6), 2.59 (s, 3), 4.07 (br s, 4), 7.53-7.57 (m, 1), 7.61 (t, 2, J=7.7), 7.87 (d, 2, J=7.5), 12.07 (s, 1), 14.56 (s, 1). MS m/z: 311 (M+1 for free base). Anal. Calcd for C18H19FN4.HCl: C, 62.33; H, 5.81; N, 16.15; Cl, 10.22. Found: C, 62.04; H, 5.95; N, 16.08; Cl, 10.02.

Provenance & Evidence