반응 #1133108

반응 방정식

cesium carbonate

2,5-dichloro-4-iodopyridine

8-amino-2-methyl-3,4-dihydroisoquinolin-1-one

→

8-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

수율 72.0%

용매

dioxane

반응 조건

후처리

1. 1
   온도to cool to room temperature
2. 2
   여과The mixture was filtered
3. 3
   기타evaporated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in EtOAc (100 mL)
5. 5
   세척washed sequentially with a saturated solution of NaHCO3 (50 mL), water (50 mL)
6. 6
   기타The organic layer was separated
7. 7
   건조dried over MgSO4
8. 8
   기타evaporated
9. 9
   기타The residue was triturated with Et2O
10. 10
    기타to leave a solid
11. 11
    기타The solid was purified by chromatography on silica
12. 12
    세척eluting with a gradient of 0-5% MeOH in CH2Cl2
13. 13
    workup.ADDITIONFractions containing product
14. 14
    기타evaporated

실험 절차

Palladium(II) acetate (0.093 g, 0.41 mmol) was added to 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.360 g, 0.62 mmol), cesium carbonate (6.76 g, 20.74 mmol), 2,5-dichloro-4-iodopyridine (2.84 g, 10.37 mmol) and 8-amino-2-methyl-3,4-dihydroisoquinolin-1-one (1.827 g, 10.37 mmol) in dioxane (100 mL) under an atmosphere of nitrogen. The resulting suspension was heated at 80° C. for 18 hours then allowed to cool to room temperature. The mixture was filtered and then evaporated. The residue was dissolved in EtOAc (100 mL), and washed sequentially with a saturated solution of NaHCO3 (50 mL), water (50 mL), and finally with a saturated solution of NaCl (50 mL). The organic layer was separated, dried over MgSO4, and then evaporated. The residue was triturated with Et2O to leave a solid. The solid was purified by chromatography on silica, eluting with a gradient of 0-5% MeOH in CH2Cl2. Fractions containing product were combined and evaporated to afford 8-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one (2.398 g, 72% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 2.97 (2H, t), 3.05 (3H, s), 3.57 (2H, t), 7.00 (1H, m), 7.34 (1H, s), 7.44-7.51 (2H, m), 8.31 (1H, s), 11.63 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=322.29 and 324.28 and 326.29.

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