Reaktion #536890

Reaktionsgleichung

6-chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate

xPhos

potassium phosphate

→

2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Ausbeute 75.6%

Lösungsmittel

butanol water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas degassed with nitrogen for 10 minutes
2. 2
   SonstigeThe crude reaction mixture
3. 3
   Extraktionwas extracted with DCM
4. 4
   Waschenwashed with water
5. 5
   Trocknendried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   Sonstigeto form a solid
9. 9
   Einengenduring concentration
10. 10
    SonstigeThis solid was triturated with ether
11. 11
    Sonstigeto afford 1.67 g of crude product
12. 12
    Sonstigepurified by silica chromatography

Vorschrift

A mixture of 6-chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (1.06 g, 3.18 mmol), potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate (1.51 g, 3.18 mmol), xPhos (227 mg, 476 μmol) and potassium phosphate (1.48 g, 6.99 mmol) in 60 ml of butanol/water (5:1) was degassed with nitrogen for 10 minutes and bis(dibenzylideneacetone)palladium (0) (137 mg, 238 mmol) was added. The reaction mixture was heated to 110° C. for 3 hr. The crude reaction mixture was extracted with DCM, washed with water, dried over Na2SO4, filtered and concentrated to form a solid during concentration. This solid was triturated with ether to afford 1.67 g of crude product. Combined with 300 mg of crude material from a previous batch and purified by silica chromatography to afford 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.6 g) as a white solid.

Quelle