Piperidine → HCID 178423329, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing [1-(4-chlorophenyl)-2-fluorovinyl]pyrrolidine (freshly prepared before use from 1-(4-chlorophenyl)-2-fluoroethan-1-one (Example 153(a)), pyrrolidine and TiCl4 (see Example 30) (3.00 g, 13.3 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.80 g, 13.3 mmol), N,N-diisopropylethylamine (2.3 mL, 13.3 mmol), piperidine (2.1 mL, 21.3 mmol), NEt3 (2.2 mL) and SnCl2 (40 mL of a 2 M soln in DMF). In this example, the SnCl2 solution was added to the reaction mixture at 140° C. (Note: When both the piperidine displacement and the SnCl2 reduction sequences are performed at 140° C. the pyrrolidine moiety is incorporated). 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 50:50 EtOAc/hexanes as eluant to give 0.38 g (8%) of 2-methyl-6-phenyl-4-piperidyl-7-pyrrolidinylpyrrolo[3,2-d]pyrimidine as a brown colored solid. This compound (0.38 g, 1.00 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.00 mL, 1.00 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×5 mL), Et2O (3×5 mL) and dried under vacuum at 60° C. to give 162 mg (2%) of the title compound as a beige colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): 1.49 (br s, 2), 1.54 (br s, 4), 1.88 (br s, 2), 2.01 (br s, 2), 2.59 (s, 3), 2.92 (br s, 4), 3.72 (br s, 2), 4.04 (br s, 2), 7.57 (d, 2, J=8.5), 7.76 (d, 2, J=8.4), 11.44 (s, 1), 13.13 (s, 1). MS m/z: 396 (M+1 for free base). Anal. Calcd for C22H26ClN4.HCl.0.5H2O: C, 59.86; H, 6.39; N, 15.87; Cl, 16.06. Found: C, 59.56; H, 6.36; N, 15.70; Cl, 15.95.

Provenance & Evidence