Hydrochloric Acid → HCID 178430021, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing (1-(3,5-difluorophenyl)prop-1-enyl) pyrrolidine (freshly prepared before use from 3,5-difluoropropiophenone (Lancaster Chemical Company), pyrrolidine and TiCl4 (2.29 g, 10.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.10 g, 10.3 mmol), N,N-diisopropylethylamine (1.8 mL, 10.3 mmol), piperidine (1.6 mL, 16.4 mmol), NEt3 (1.6 mL) and SnCl2 (31 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 give605 mg (17%) of 6-(3,5-difluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored foam. This compound (600 mg, 1.75 mmol) was dissolved in 10:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.80 mL, 1.80 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 291 mg (7%) of the title compound as a beige colored solid. Mp: 242-245° C. 1H HMR (DMSO-d6; 400 MHz): δ 1.52 (br s, 6), 2.28 (s, 3), 2.55 (s, 3), 3.97 (br s, 4), 7.36-7.41 (m, 3), 11.89 (s, 1), 13.82 (s, 1). MS m/z: 343 (M+1 for free base). Anal. Calcd for C19H20F2N4.HCl.0.5H2O: C, 58.83; H, 5.72; N, 14.45; Cl, 9.24. Found: C, 58.86; H, 5.72; N, 14.50; Cl, 9.29.

Provenance & Evidence