Piperidine → HCID 178423294, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing 1-(methylsulfonyl)-4-(1-pyrrolidinylvinyl) benzene (freshly prepared before use from 3-methyl sulfonylacetophenone (Acros Chemical Company), pyrrolidine and TiCl4 (2.01 g, 8.00 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.71 g, 8.00 mmol), N,N-diisopropylethylamine (1.4 mL, 8.0 mmol), piperidine (1.3 mL, 12.8 mmol), NEt3 (1.4 mL) and SnCl2 (24 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 1.10 g (37%) of 1-[2-methyl-4-piperidyl pyrrolo[4,5-d]pyrimidin-6-yl]-4-(methylsulfonyl)benzene as a beige colored solid. This compound (1.10 g, 2.97 mmol) was dissolved in 4:1 EtOAc/MeOH (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (3.00 mL, 3.00 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 1.05 g (32%) of the title compound as a beige colored solid. Mp: 279-281° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 3.23 (s, 3), 4.01 (br s, 4), 7.02 (s, 1), 7.93, 8.27 (AB q, 4, J=8.3, 8.3), 12.14 (s, 1), 14.38 (s, 1). MS m/z: 371 (M+1 for free base). Anal. Calcd for C19H22N4O2S.HCl.H2O: C, 53.70; H, 5.93; N, 13.19; Cl, 8.34. Found: C, 53.82; H, 5.94; N, 13.08; Cl, 8.49.

Provenance & Evidence