Reaktion #742293

Reaktionsgleichung

potassium carbonate

(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)propanamide mesylate

THF

methanesulfonic acid

→

(2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-(3-hydroxyazetidin-1-yl)-N-(5-methylpyrazin-2-yl)propanamide

Lösungsmittel

tert-Butyl methyl ether

water

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGwith stirring
2. 2
   SonstigeThe aqueous phase was removed
3. 3
   Waschenthe organic phase was washed with water (20.0 mL)
4. 4
   Sonstigethen evaporated under reduced pressure at 50° C
5. 5
   workup.ADDITIONTHF (80 mL) was added to the residue
6. 6
   Sonstigeremoved by evaporation under reduced pressure
7. 7
   workup.ADDITIONTHF (20.0 mL) was added to the residue
8. 8
   FiltrationThe mixture was filtered
9. 9
   workup.STIRRINGthen stirred whilst cyclohexane (50.0 mL)
10. 10
    workup.ADDITIONwas added dropwise
11. 11
    FiltrationThe solid was collected by filtration
12. 12
    Waschenwashed with a mixture tert-butyl methyl ether (50.0 mL) and cyclohexane (50.0 mL)
13. 13
    Sonstigedried

Vorschrift

A mixture of (S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)propanamide mesylate (16.5 g), THF (50.00 mL), water (20.0 mL) and methanesulfonic acid (2.62 g) was stirred for 19 hours at ambient temperature. tert-Butyl methyl ether (40.0 mL) was added followed by the dropwise addition of a solution of potassium carbonate (3.77 g) in water (20.0 mL) over 20 mins with stirring. The aqueous phase was removed and the organic phase was washed with water (20.0 mL) then evaporated under reduced pressure at 50° C. THF (80 mL) was added to the residue and then removed by evaporation under reduced pressure. This process was repeated. THF (20.0 mL) was added to the residue followed by tert-butyl methyl ether (60.0 ml). The mixture was filtered then stirred whilst cyclohexane (50.0 mL) was added dropwise. The solid was collected by filtration and washed with a mixture tert-butyl methyl ether (50.0 mL) and cyclohexane (50.0 mL) and dried to give (2S)-2-[1-(2,6-dichlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-(3-hydroxyazetidin-1-yl)-N-(5-methylpyrazin-2-yl)propanamide in an overall yield for steps a) and b) of 69%.

Quelle