反応 #44237

反応方程式

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

2-fluoro-4-methylthioaniline

BINAP

Cs2CO3

N2

→

desired product

収率 42.4%

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

収率 42.4%

溶媒

EtOAc

toluene

反応条件

後処理

1. 1
   温度heated at 80° C. for 16 hours
2. 2
   workup.STIRRINGwith stirring
3. 3
   温度The reaction mixture was cooled to room temperature
4. 4
   ろ過The precipitate was filtered off
5. 5
   洗浄washed with EtOAc
6. 6
   洗浄The filtrate was washed with water
7. 7
   その他The organic layer was separated
8. 8
   抽出the aqueous layer was extracted with EtOAc
9. 9
   乾燥The combined organic layers were dried over MgSO4
10. 10
    ろ過filtered
11. 11
    濃縮concentrated
12. 12
    その他to give the crude material that
13. 13
    その他was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

実験手順

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.

出典