Reaktion #44237

Reaktionsgleichung

methyl 4-chloro-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate

2-fluoro-4-methylthioaniline

BINAP

Cs2CO3

N2

→

desired product

Ausbeute 42.4%

methyl 4-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate

Ausbeute 42.4%

Lösungsmittel

EtOAc

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheated at 80° C. for 16 hours
2. 2
   workup.STIRRINGwith stirring
3. 3
   TemperaturThe reaction mixture was cooled to room temperature
4. 4
   FiltrationThe precipitate was filtered off
5. 5
   Waschenwashed with EtOAc
6. 6
   WaschenThe filtrate was washed with water
7. 7
   SonstigeThe organic layer was separated
8. 8
   Extraktionthe aqueous layer was extracted with EtOAc
9. 9
   TrocknenThe combined organic layers were dried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    Sonstigeto give the crude material that
13. 13
    Sonstigewas purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

Vorschrift

A mixture solution of methyl 4-chloro-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate (72 mg, 0.35 mmol), 2-fluoro-4-methylthioaniline (69 mg, 0.44 mmol), Pd(OAc)2 (10 mg, 0.044 mmol), BINAP (40 mg, 0.064 mmol), and Cs2CO3 (197 mg, 0.60 mmol) in toluene (1.5 mL) was sealed in a vial under N2 atmosphere. It was stirred for 10 minutes at room temperature and then heated at 80° C. for 16 hours with stirring. The reaction mixture was cooled to room temperature and diluted with EtOAc. The precipitate was filtered off and washed with EtOAc. The filtrate was washed with water. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, concentrated to give the crude material that was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2) followed by additional silica gel flash column chromatography (10 to 15 to 20% EtOAc in CH2Cl2) to afford 48 mg (42%) of the desired product.

Quelle