Piperidine → HCID 178423293, compound

Participants

Reaction Conditions

Reaction Steps

Using the method described in Example 30 by employing trifluoro[4-(1-pyrrolidinylvinyl)phenylthio]methane (freshly prepared before use from 4′-(trifluoro methylthio)acetophenone (Oakwood Products Inc.), pyrrolidine and TiCl4 (1.96 g, 7.17 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.50 g, 7.17 mmol), N,N-diisopropylethylamine (1.2 mL, 7.17 mmol), piperidine (1.1 mL, 11.5 mmol), NEt3 (1.1 mL) and SnCl2 (21 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 742 mg (26%) of trifluoro[4-(2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl)phenylthio]methane as a beige colored foam. This compound (741 mg, 1.90 mmol) was dissolved in 10:1 EtOAc/MeOH (60 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 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 418 mg (13%) of the title compound as white colored needles. Mp: 270-272° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.65 (br s, 6), 2.51 (s, 3), 4.00 (br s, 4), 6.96 (s, 1), 7.84 (d, 2, J=8.1), 8.06 (d, 2, J=8.2), 12.12 (s, 1), 14.39 (s, 1). MS m/z: 393 (M+1 for free base). Anal. Calcd for C19H19F3N4S.HCl.H2O: C, 51.06; H, 4.96; N, 12.54; Cl, 7.93. Found: C, 51.02; H, 4.98; N, 12.46; Cl, 8.02.

Provenance & Evidence