Reacción #62178

Ecuación de reacción

NaOH

3-Fluoro-4-(1-methyl-4-pyridin4-yl-1H-pyrazol-3-yl)-phenol

cesium carbonate

2-chloro methyl quinoline

→

title compound

2-[3-Fluoro-4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted with methylene chloride, dried magnesium sulfate
2. 2
   Filtraciónfiltered
3. 3
   Concentraciónconcentrated
4. 4
   OtroBiotage MPLC purification
5. 5
   Lavadoeluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes

Procedimiento

To a solution of 3-Fluoro-4-(1-methyl-4-pyridin4-yl-1H-pyrazol-3-yl)-phenol (450 mg) in dimethylformamide (10 ml) was added cesium carbonate (2 g) and 2-chloro methyl quinoline (481 mg) and the reaction mixture was heated at 60° C. for 18 h. The reaction mixture was poured into 1N NaOH, extracted with methylene chloride, dried magnesium sulfate, filtered and concentrated. Biotage MPLC purification eluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes provided the title compound. The free base was stirred in ethyl acetate and 1.1 equivalents of succinic acid was added. The white precipitate was filtered and dried to provide the title compound as the succinate salt (280 mg). 1H NMR (400 MHz, DMSO) δ 8.43 (d, J=8.3 Hz, 1 H), 8.37 (d, J=6.2 Hz, 2H), 8.26 (s, 1H), 8.00 (m, 2H), 7.78 (t, J=7.1 Hz, 1H), 7.70 (d, J=8.3 Hz, 1 H), 7.61 (t, J=6.6 Hz, 1 H), 7.38 (t, J=8.3, Hz, 1 H), 7.10 (d, J=6.2 Hz, 2H), 7.00 (m, 2H), 5.40 (s, 2H), 3.88 (s, 3 H), 2.38 (s, 4H), MS: (M+H m/z=411.1).

Fuente