Piperidine → HCID 178423331, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 1-[(2-pyrrolidinylprop-1-enyl)sulfonyl]-4-chlorobenzene (freshly prepared before use from 4-chlorophenylsulfonylacetone (Lancaster Chemical Company), pyrrolidine and TiCl4 (2.03 g, 7.10 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.47 g, 7.10 mmol), N,N-diisopropylethylamine (1.3 mL, 7.10 mmol), piperidine (1.1 mL, 11.4 mmol), NEt3 (1.6 mL) and SnCl2 (21 mL of a 2 M soln in DMF). In this example the mixture of enamine, 2-methyl-4,6-dichloro-5-nitropyrimidine and N,N-diisopropylethylamine was stirred at 100° C. for 20 h prior to piperidine addition. 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 100% EtOAc as eluant to give 441 g (15%) of 4-chloro-1-[((2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)methyl)sulfonyl]benzene as a brown colored solid. This compound (0.44 g, 1.08 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.10 mL, 1.10 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 296 mg (9%) of the title compound as a white colored solid. Mp: 199-201° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.57 (m, 4), 1.65 (m, 2), 2.47 (s, 3), 3.85 (br s, 4), 5.02 (s, 2), 6.23 (s, 1), 7.65 (AB q, 4, J=6.2, 6.2), 12.20 (s, 1), 14.18 (s, 1). MS m/z: 405 (M+1 for free base). Anal. Calcd for C19H21ClN4O2S.HCl.0.9H2O: C, 49.87; H, 5.24; N, 12.25; Cl, 15.49. Found: C, 49.85; H, 5.17; N, 12.15; Cl, 15.61.

Provenance & Evidence