Piperidine → HCID 178423295, Verbindung

Using the method described in Example 30 by employing [1-(3,4,5-trifluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 3,4,5-trifluoro acetophenone (Oakwood Products Inc.), pyrrolidine and TiCl4 (1.58 g, 6.96 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.40 g, 6.96 mmol), N,N-diisopropylethylamine (1.2 mL, 6.96 mmol), piperidine (1.1 mL, 11.1 mmol), NEt3 (1.1 mL) and SnCl2 (21 mL of a 2 M soln in DMF). In this example the 2 M SnCl2 solution was added to the reaction mixture at 140° C. Heating was then discontinued and the mixture was allowed to cool to room temperature. The mixture was stirred at room temperature for an additional 48 h. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 620 mg (26%) of 2-methyl-4-piperidyl-6-(3,4,5-trifluorophenyl)pyrrolo[3,2-d]pyrimidine as a beige colored gummy solid. This compound (621 mg, 1.80 mmol) was dissolved in 3:1 EtOAc/MeOH (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.80 mL, 1.80 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 426 mg (16%) of the title compound as a white colored fluffy solid. Mp: >280° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.07 (s, 4), 7.07 (s, 1), 8.14 (m, 2), 12.04 (s, 1), 14.45 (s, 1). MS m/z: 347 (M+1 for free base). Anal. Calcd for C18H17F3N4.HCl.0.5H2O: C, 55.23; H, 4.88; N, 14.32; Cl, 9.06. Found: C, 55.23; H, 4.86; N, 14.11; Cl, 9.06.

1. customwas added to the reaction mixture at 140° C
2. temperatureHeating
3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

ORD-Eintrag

ord-7d1883f2b359497e8a42c538e03e1f21

Quelldatensatz

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06583154B1