반응 #678952

반응 방정식

2-amino-4,6-difluoro-benzamide

3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde

sodium hydrogen sulfite

p-toluenesulfonic acid monohydrate

→

title compound

2-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-difluoroquinazolin-4(3H)-one

용매

N,N-dimethylacetamide

반응 조건

후처리

1. 1
   온도cooled to room temperature
2. 2
   기타Solvent was evaporated under reduced pressure
3. 3
   workup.ADDITIONWater (50 mL) was added
4. 4
   추출The mixture was extracted with CH2Cl2 (2×100 mL)
5. 5
   세척washed with water
6. 6
   기타The organic phase was evaporated
7. 7
   세척the residue was washed with hexane/ether (90:10, 100 mL)
8. 8
   여과The solid was filtered
9. 9
   기타dried under vacuum

실험 절차

To a solution of 2-amino-4,6-difluoro-benzamide (0.80 g, 4.60 mmol) and 3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde (1.14 g, 4.60 mmol) in N,N-dimethylacetamide (60 mL) were added sodium hydrogen sulfite (58.5 wt %, 1.25 g, 6.9 mmol) and p-toluenesulfonic acid monohydrate (3.50 g, 18.4 mmol). The reaction mixture was stirred at 145° C. for 16 hours under nitrogen atmosphere, then cooled to room temperature. Solvent was evaporated under reduced pressure. Water (50 mL) was added, followed by saturated aqueous sodium bicarbonate solution (15 mL). The mixture was extracted with CH2Cl2 (2×100 mL) and washed with water. The organic phase was evaporated and the residue was washed with hexane/ether (90:10, 100 mL). The solid was filtered and dried under vacuum to give the title compound as a brown solid. Yield: 1.48 g (80%). MP 234-235° C. 1H NMR (400 MHz, DMSO-d6): δ 12.36 (s, 1H), 7.90 (s, 1H), 7.32 (m, 2H), 3.91 (t, J=4 Hz, 2H), 2.83 (t, J=4 Hz, 2H), 2.55 (s, 4H), 2.31 (s, 6H), 1.70 (s, 4H).

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