Reacción #90819

Ecuación de reacción

DPEPhos

DPEPhos

3-Methyl-1-(1-methylethyl)-1H-pyrazol-5-amine

cesium carbonate

2,5-dichloro-4-iodopyridine

2-amino-3-fluorobenzonitrile

potassium triphosphate

→

2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrile

Rendimiento 53.4%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaat reflux for 18 hr
2. 2
   FiltraciónThe reaction mixture was filtered
3. 3
   OtroThe reaction mixture was degassed
4. 4
   TemperaturaThe reaction mixture was refluxed overnight
5. 5
   FiltraciónThe reaction mixture was filtered
6. 6
   workup.DISSOLUTIONthe solid was dissolved in water
7. 7
   workup.STIRRINGstirred for 10 minutes
8. 8
   Filtraciónfiltered again

Procedimiento

To a degassed solution of 2,5-dichloro-4-iodopyridine (8 g, 29.2 mmol), 2-amino-3-fluorobenzonitrile (3.98 g, 29.2 mmol) and potassium triphosphate (18.60 g, 88 mmol) in 1,4-dioxane (60 ml) stirred under nitrogen at the room temperature was added DPEPhos (1.258 g, 2.337 mmol) and palladium acetate (0.262 g, 1.168 mmol) The reaction mixture was stirred at reflux for 18 hr. The reaction mixture was filtered. 3-Methyl-1-(1-methylethyl)-1H-pyrazol-5-amine (4.07 g, 29.2 mmol) and cesium carbonate (28.6 g, 88 mmol) were added. The reaction mixture was degassed and palladium acetate (0.262 g, 1.168 mmol) and DPEPhos (1.258 g, 2.337 mmol) were added. The reaction mixture was refluxed overnight. The reaction mixture was filtered and the solid was dissolved in water, heated to 50° C. and stirred for 10 minutes, then filtered again. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzonitrile (6 g, 15.59 mmol, 53.4% yield) was isolated as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (d, J=6.57 Hz, 6 H) 2.07 (s, 3 H) 4.32 (quin, J=6.57 Hz, 1 H) 5.64 (d, J=2.02 Hz, 1 H) 5.83 (s, 1 H) 7.39-7.58 (m, 1 H) 7.63-7.82 (m, 2 H) 7.88 (s, 1 H) 8.26 (br. s., 1 H) 8.41 (br. s., 1 H); HPLC Rt=2.35 min, MS (ESI): 385.0 [M+H]+.

Fuente