Реакция #46388

Уравнение реакции

compound

1-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone

potassium trifluoroacetate

toluene

water ether

→

title product

Выход 0.3%

1-[5-(4-Fluoro-phenyl)-2-methyl-thiazol-4-yl]-1-{(S)-2-[(5-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-methanone

Выход 0.3%

Растворители

dimethylformamide

Условия реакции

Обработка

1. 1
   Температураthe resulting mixture heated
2. 2
   Температураat reflux under Dean-Stark conditions for 3 h
3. 3
   Температураbefore refluxing for a further 20 h
4. 4
   ТемператураThe reaction mixture was cooled
5. 5
   Фильтрацияfiltered through kieselguhr
6. 6
   ЭкстракцияThe aqueous layer from the filtrate was extracted with ether
7. 7
   Промывкаthe combined ether extracts washed with water
8. 8
   Другоеdried
9. 9
   Другоеevaporated
10. 10
    ЭкстракцияThe aqueous was re-extracted with dichloromethane
11. 11
    Другоеthe extract evaporated
12. 12
    ДругоеThe combined extracts were chromatographed on silica gel
13. 13
    Промывкаeluting with methanol-dichloromethane mixtures

Методика

To the compound from Example 194 (0.36 g) in dimethylformamide (5 ml) was added potassium trifluoroacetate (0.23 g), copper iodide (0.3 g) and toluene (5 ml) and the resulting mixture heated at reflux under Dean-Stark conditions for 3 h, before refluxing for a further 20 h. The reaction mixture was cooled, poured into water/ether and filtered through kieselguhr. The aqueous layer from the filtrate was extracted with ether, and the combined ether extracts washed with water, dried and evaporated. The aqueous was re-extracted with dichloromethane and the extract evaporated. The combined extracts were chromatographed on silica gel, eluting with methanol-dichloromethane mixtures, to afford the title product (0.001 g). Mass Spectrum (Electrospray LC/MS): Found 466 (MH+). C21H19F4N5OS requires 465.

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