Reaction #84655

Reaction equation

2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline

tert-butyl ((1S,2S)-2-aminocyclohexyl)carbamate

Cs2CO3

X-Phos

→

tert-butyl ((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)carbamate

Yield 45.3%

Solvents

DMA

Conditions

Workup

1. 1
   Otherwas degassed with N2 for 5 mins
2. 2
   TemperatureThe mixture was cooled to room temperature
3. 3
   Filtrationfiltered through celite
4. 4
   Washwashed with water
5. 5
   OtherThe residue was purified by silica gel column chromatography

Procedure

A mixture of 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (0.1 g, 0.27 mmol), tert-butyl ((1S,2S)-2-aminocyclohexyl)carbamate (75 mg, 0.35 mmol), Cs2CO3 (176 mg, 0.54 mmol), X-Phos (13 mg, 0.027 mmol) and Pd2dba3 (12.5 mg, 0.013 mmol) in DMA (1.8 mL) was degassed with N2 for 5 mins and heated in a microwave reactor at 125° C. for 30 mins. The mixture was cooled to room temperature, filtered through celite and washed with water followed by saturated brine solution. The residue was purified by silica gel column chromatography to afford tert-butyl ((1S,2R)-2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)cyclohexyl)carbamate (67 mg, 45%). MS (ES+) C27H32Cl2N4O4 requires: 546, found: 547 [M+H]+.

Source