Reacción #1458347

Ecuación de reacción

[1-(2,6-difluorophenyl)vinyl]pyrrolidine

2′,6′-difluoro acetophenone

pyrrolidine

2-methyl-4,6-dichloro-5-nitropyrimidine

N,N-diisopropylethylamine

piperidine

SnCl2

→

6-(2,6-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine

Rendimiento 11.0%

Disolventes

DMF

NEt3

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Procedimiento

Using the method described in Example 30 by employing [1-(2,6-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 2′,6′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.51 g, 7.22 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.20 g, 5.79 mmol), N,N-diisopropylethylamine (1.3 mL, 7.22 mmol), piperidine (1.2 mL, 11.6 mmol), NEt3 (1.2 mL) and SnCl2 (22 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 199 mg (11%) of 6-(2,6-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored powder. This material (199 mg, 0.61 mmol) was dissolved in 5:1 EtOAc/MeOH (20 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (0.60 mL, 0.60 mmol). The solution was left 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 33 mg (2%) of the title compound as a pale yellow colored sandy solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.71 (br s, 6), 2.58 (s, 3), 4.02 (s, 4), 6.77 (s, 1), 7.35 (t, 2, J=8.3), 7.67 (dquintet, 1, J=1.4, 6.8), 12.41 (s, 1), 14.51 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.2H2O: C, 55.99; H, 5.58; N, 14.51; Cl, 9.18. Found: C, 55.99; H, 5.61; N, 14.41; Cl, 9.08.

Fuente