Réaction #73383

Équation de réaction

sodium hydroxide

2,4-dichloropyrimidine

5-hydroxy-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

5-hydroxy-N-(3-(trifluoromethyl)phenyl)indoline-1-carboxamide

sodium hydroxide

→

5-(2-chloropyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Solvants

acetone

water

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGAfter additional 30 min stirring the reaction
2. 2
   Concentrationis concentrated
3. 3
   workup.ADDITIONdiluted with EtOAc
4. 4
   Lavagewashed with water and brine before the organic layer
5. 5
   Séchageis dried over sodium sulfate
6. 6
   Concentrationconcentrated
7. 7
   AutreThe residue is separated via FCC (5-50% EtOAc in heptane)

Mode opératoire

A mixture of 5-hydroxy-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide and 5-hydroxy-N-(3-(trifluoromethyl)phenyl)indoline-1-carboxamide (6:4) (3 g) is mixed with sodium hydroxide (0.45 g, 11.2 mmol) and 2,4-dichloropyrimidine (1.68 g, 11.2 mmol) in 50 mL of acetone and 50 mL of water at 0° C. and stirred for 1.5 h. Additional sodium hydroxide (0.075 g, 1.88 mmol) and (0.279 g, 1.88 mmol) are added. After additional 30 min stirring the reaction is concentrated, diluted with EtOAc, washed with water and brine before the organic layer is dried over sodium sulfate and concentrated. The residue is separated via FCC (5-50% EtOAc in heptane) to give 5-(2-chloropyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide. 1H NMR (400 MHz, CDCl3) δ ppm 8.45 (d, J=5.7 Hz, 1 H), 8.24 (d, J=9.0 Hz, 1 H), 7.86 (s, 1 H), 7.78 (d, J=8.2 Hz, 1 H), 7.60 (d, J=3.7 Hz, 1 H), 7.55 (t, J=8.0 Hz, 1 H), 7.45-7.50 (m, 2 H), 7.42 (d, J=2.1 Hz, 1 H), 7.15 (dd, J=8.9, 2.3 Hz, 1 H), 6.82 (d, J=5.7 Hz, 1 H), 6.73 (dd, J=3.7, 0.6 Hz, 1 H).

Source