Reacción #84638

Ecuación de reacción

tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate

(2-chloro-3-ethoxy-6-fluorophenyl)boronic acid

potassium phosphate

→

tert-butyl ((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate

Rendimiento 84.8%

Disolventes

1,4-dioxane water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed with nitrogen for 5 min
2. 2
   TemperaturaThe reaction mixture was cooled to room temperature
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   Lavadowashed with saturated ammonium chloride solution
5. 5
   Secadodried with sodium sulfate
6. 6
   OtroThe residue was purified by silica gel column chromatography

Procedimiento

A mixture of tert-butyl ((1S,2R)-2-((6-bromoquinazolin-2-yl)amino)cyclopentyl)carbamate (50 mg, 0.12 mmol), (2-chloro-3-ethoxy-6-fluorophenyl)boronic acid (40 mg, 0.18 mmol), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (4 mg, 0.005 mmol) and potassium phosphate (78 mg, 0.37 mmol) in 1,4-dioxane/water (1.15 mL/0.15 mL) was degassed with nitrogen for 5 min and stirred at 100° C. for 30 min under microwave. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated ammonium chloride solution and dried with sodium sulfate. The residue was purified by silica gel column chromatography to afford tert-butyl ((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate (51 mg, 83%). MS (ES+) C26H30ClFN4O3 requires: 500, found: 501 [M+H]+.

Fuente