تفاعل #635921

معادلة التفاعل

Cesium carbonate

3-hydroxy-N-(5-methylpyrazin-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

6-bromo-3,4-dihydro-2H-isoquinolin-1-one

2,2,6,6 tetramethyl-3,5-heptanedione

→

desired compound

N-(5-Methylpyrazin-2-yl)-3-[(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

المذيبات

NMP

ظروف التفاعل

المعالجة

1. 1
   ترشيحThe reaction mixture was filtered through diatomaceous earth
2. 2
   غسيلthe filter pad washed thoroughly with DCM and methanol
3. 3
   تركيزThe filtrate was concentrated in vacuo, water (20 mL)
4. 4
   workup.ADDITIONwas added to the residue
5. 5
   استخلاصthe mixture extracted with ethyl acetate (3×50 mL)
6. 6
   غسيلThe combined organic phases were washed with water (2×10 mL), brine (20 mL)
7. 7
   تجفيفdried (MgSO4)
8. 8
   أخرىevaporated in vacuo
9. 9
   أخرىThe crude product was chromatographed on silica
10. 10
    غسيلeluting with a gradient of 0-5% methanol in DCM

الإجراء التجريبي

Cesium carbonate (812 mg, 2.50 mmol) was added to a solution of 3-hydroxy-N-(5-methylpyrazin-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (262 mg, 0.83 mmol), 6-bromo-3,4-dihydro-2H-isoquinolin-1-one (226 mg, 1.0 mmol), copper (I) iodide (158 mg, 0.83 mmol) and 2,2,6,6 tetramethyl-3,5-heptanedione (0.7 mL, 3.3 mmol) in NMP (9 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 8 hours. The reaction mixture was filtered through diatomaceous earth and the filter pad washed thoroughly with DCM and methanol. The filtrate was concentrated in vacuo, water (20 mL) was added to the residue and the mixture extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with water (2×10 mL), brine (20 mL), dried (MgSO4) and evaporated in vacuo. The crude product was chromatographed on silica, eluting with a gradient of 0-5% methanol in DCM, to give the desired compound a white solid (190 mg). 1H NMR δ (CDCl3): 2.17 (1H, m), 2.22-2.29 (1H, m), 2.56 (3H, s), 2.94-3.02 (2H, m), 3.49-3.59 (2H, m), 3.90-4.01 (4H, m), 5.00 (1H, s), 6.01 (1H, s), 6.77-6.80 (1H, m), 6.83 (1H, s), 6.96 (1H, d), 7.16 (1H, s), 7.26 (1H, d), 8.06 (1H, d), 8.15 (1H, s), 8.49 (1H, s), 9.54 (1H, s); m/z 461 (M+H)+, 459 (M−H)−

المصدر