반응 #44237

반응 방정식

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

2-fluoro-4-methylthioaniline

BINAP

Cs2CO3

N2

→

desired product

수율 42.4%

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

수율 42.4%

용매

EtOAc

toluene

반응 조건

후처리

1. 1
   온도heated at 80° C. for 16 hours
2. 2
   workup.STIRRINGwith stirring
3. 3
   온도The reaction mixture was cooled to room temperature
4. 4
   여과The precipitate was filtered off
5. 5
   세척washed with EtOAc
6. 6
   세척The filtrate was washed with water
7. 7
   기타The organic layer was separated
8. 8
   추출the aqueous layer was extracted with EtOAc
9. 9
   건조The combined organic layers were dried over MgSO4
10. 10
    여과filtered
11. 11
    농축concentrated
12. 12
    기타to give the crude material that
13. 13
    기타was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

실험 절차

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.

출처