Reacción #62108

Ecuación de reacción

2-[4-(4-Pyridin4-yl-2H-pyrazol-3-yl)-phenoxymethyl}-quinoline

1,1,1-Trifluoro-2-iodo-ethane

cesium carbonate

→

title compound

2-{4-[-Pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline

Disolventes

dimethyl formamide

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted 3× methylene chloride
2. 2
   Secadodried with magnesium sulfate
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated
5. 5
   OtroPurification via flash chromatography
6. 6
   Lavadoeluting with 5% methanol/70% ethyl acetate/hexanes

Procedimiento

To a solution of 2-[4-(4-Pyridin4-yl-2H-pyrazol-3-yl)-phenoxymethyl}-quinoline (26.5 g) in dimethyl formamide (140 mL) was added 1,1,1-Trifluoro-2-iodo-ethane (21 mL, 2.0 eq.) and cesium carbonate (68.3 g, 3 eq.) and the reaction mixture heated at 60° C. for 24 h. The reaction mixture was diluted with water, extracted 3× methylene chloride, dried with magnesium sulfate, filtered and concentrated. Purification via flash chromatography eluting with 5% methanol/70% ethyl acetate/hexanes provided the title compound 20.85 g as an 8:1 regioisomeric mixture. Preparative HPLC eluting with acetonitile/methanol (98:2) on a chiralpak AD column with a flow rate of 430 ml/Min provided the pure title compound as a free base 13.4 g. 1H NMR (400 MHz, CDCl3) δ 8.45 (m, 2 H), 8.16 (d, J=8.3 Hz, 1 H), 8.04 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.79 (d, J=8.3 Hz, 1 H), 7.69 (m, 1 H), 7.64 (d, J=8.3 Hz, 1 H), 7.50 (m, 1H), 7.36 (d, J=8.7 Hz, 2 H), 7.14 (d, J=6.2 Hz, 2H), 6.98 (d, J=9.1 Hz, 2 H), 5.35 (s, 2H), 4.75 (q, J=8.3 Hz, 2 H); MS: (M+H m/z=427.1).MS: (M+H m/z=461.2).

Fuente