Réaction #84649

Équation de réaction

2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-aminobicyclo[3.1.0]hexan-3-ylcarbamate

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

sodium bicarbonate

→

title compound

Rendement 62.5%

2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamate

Rendement 62.5%

Solvants

N-methyl-2-pyrrolidone

ethyl acetate

Conditions de réaction

Traitement

1. 1
   Lavagewashed with water (eight times) and brine (50 mL)
2. 2
   SéchageThe organic layer was dried over sodium sulfate
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated
5. 5
   Autreto afford a crude product, which
6. 6
   Autrewas purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2)

Mode opératoire

A solution of 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-aminobicyclo[3.1.0]hexan-3-ylcarbamate (250 mg, 0.977 mmol), 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (300 mg, 0.814 mmol) and sodium bicarbonate (205 mg, 2.442 mmol) in N-methyl-2-pyrrolidone (10 mL) was stirred at 100° C. overnight. The reaction solution was cooled to room temperature, diluted with ethyl acetate (100 mL) and washed with water (eight times) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to afford a crude product, which was purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2) to afford the title compound (300 mg, 52%) as a yellow solid. MS (ES+) C28H34Cl2N4O4Si requires: 588, 590, found: 589, 591 [M+H]+.

Source