反应详情

温度

0 °C

Sodium hydride (38.5 mg, 0.96 mmol) was added to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-chloropyridin-2-yl)-2-hydroxypropanamide (Intermediate AU3) (200 mg, 0.40 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 7-chloro-3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (Intermediate AP2) (107 mg, 0.40 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The reaction mixture was diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (25 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% EtOAc in isohexane to give (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(3-(2-chlorophenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yloxy)-N-(5-chloropyridin-2-yl)propanamide (290 mg, 99%). m/z (ES+), (M+H)+=728.38: HPLC tR=3.91 min Intermediate AP5: 6-chloro-N4-o-tolylpyrimidine-4,5-diamine

1. temperatureto warm to room temperature
2. stirringstirred for 1 hour
3. customthe majority of the THF removed in vacuo
4. additionThe reaction mixture was diluted with water (20 mL) and EtOAc (50 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer re-extracted with EtOAc (2×50 mL)
7. washThe combined organics were washed with saturated brine (25 mL)
8. dry with materialdried (MgSO4)
9. customevaporated
10. customThe crude product was purified by flash silica chromatography
11. washeluting with 0 to 50% EtOAc in isohexane