Réaction #44237

Équation de réaction

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

2-fluoro-4-methylthioaniline

BINAP

Cs2CO3

N2

→

desired product

Rendement 42.4%

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

Rendement 42.4%

Solvants

EtOAc

toluene

Conditions de réaction

Traitement

1. 1
   Températureheated at 80° C. for 16 hours
2. 2
   workup.STIRRINGwith stirring
3. 3
   TempératureThe reaction mixture was cooled to room temperature
4. 4
   FiltrationThe precipitate was filtered off
5. 5
   Lavagewashed with EtOAc
6. 6
   LavageThe filtrate was washed with water
7. 7
   AutreThe organic layer was separated
8. 8
   Extractionthe aqueous layer was extracted with EtOAc
9. 9
   SéchageThe combined organic layers were dried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated
12. 12
    Autreto give the crude material that
13. 13
    Autrewas purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

Mode opératoire

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.

Source