2-Methylpiperidine → HCID 178433067, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing [1-(4-fluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 4′-fluoroacetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (2.17 g, 11.4 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (2.42 g, 11.4 mmol), N,N-diisopropylethylamine (2.0 mL, 11.4 mmol), 2-methylpiperidine (2.1 mL, 18.2 mmol), NEt3 (2.0 mL) and SnCl2 (34 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 0.88 g (24%) of 6-(4-fluorophenyl)-2-methyl-4-(2-methylpiperidyl)pyrrolo[3,2-d]pyrimidine as a beige colored solid. This compound (882 mg, 2.71 mmol) was dissolved in 10:1 EtOAc/MeOH (50 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 573 mg (14%) of the title compound as a white colored solid. Mp: 274-276° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.20 (d, 3, J=6.9), 1.40-1.73 (m, 6), 2.44 (s, 3), 3.35 (br s, 1), 4.48 (br s, 1), 5.13 (br s, 1), 6.75 (s, 1), 7.28 (t, 2, J=8.9), 7.89 (dd, 2, J=5.4, 5.4), 11.79 (s, 1), 14.04 (s, 1). MS m/z: 325 (M+1 for free base). Anal. Calcd for C19H21FN4.HCl.H2O: C, 60.23; H, 6.39; N, 14.79; Cl, 9.36. Found: C, 60.60; H, 6.28; N, 14.90; Cl, 9.35.

Provenance & Evidence