反応 #70681

反応方程式

1,4-dioxane

6-Bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide

1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine

potassium phosphate

→

title compound

N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide

溶媒

water

反応条件

後処理

1. 1
   その他degassed under N2 for 15 min. (emulsion)
2. 2
   その他degassed for 2 min
3. 3
   その他The reaction flask was sealed
4. 4
   温度the contents heated
5. 5
   温度at reflux for 2 h
6. 6
   ろ過The suspension was filtered
7. 7
   その他dioxane was removed in vacuo
8. 8
   その他The resultant oil was partitioned between 300 mL of ethyl acetate and 100 mL of water
9. 9
   その他the layers were separated
10. 10
    workup.ADDITIONDecolorizing carbon was added
11. 11
    ろ過the organic layer was filtered through short pad of silica
12. 12
    workup.ADDITION300 mL of 1 M HCl was added
13. 13
    抽出The contents were extracted with ethyl acetate
14. 14
    その他The organic layer was separated
15. 15
    洗浄washed with brine
16. 16
    乾燥dried over MgSO4
17. 17
    ろ過filtered
18. 18
    濃縮concentrated in vacuo
19. 19
    ろ過filtered

実験手順

6-Bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide (1.9 g, 4.42 mmol), 1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (1.277 g, 4.42 mmol) and potassium phosphate (tribasic) (2.81 g, 13.25 mmol) were placed in a 150 mL pressure vessel followed by addition of 1,4-dioxane (40 mL) and water (10.00 mL). The suspension was stirred and degassed under N2 for 15 min. (emulsion). Next added in PdCl2(dppf)-CH2Cl2 adduct (0.361 g, 0.442 mmol) and degassed for 2 min. The reaction flask was sealed and the contents heated at reflux for 2 h. The suspension was filtered, and dioxane was removed in vacuo. The resultant oil was partitioned between 300 mL of ethyl acetate and 100 mL of water, and the layers were separated. Decolorizing carbon was added, and after 10 min, the organic layer was filtered through short pad of silica. 300 mL of 1 M HCl was added and neutralized with NaOH (to pH ˜9). The contents were extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The product was suspended in diethyl ether and filtered. The title compound was isolated as a yellow solid (950 mg, 41% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.49 (br. s., 1H), 8.52 (d, J=2.27 Hz, 1H), 8.15 (t, J=5.05 Hz, 1H), 7.95 (dd, J=2.53, 8.84 Hz, 1H), 7.73 (d, J=1.26 Hz, 1H), 7.29 (s, 1H), 7.19 (d, J=1.52 Hz, 1H), 6.93 (d, J=9.09 Hz, 1H), 5.87 (s, 1H), 4.85 (quin, J=6.63 Hz, 1H), 4.35 (d, J=5.05 Hz, 2H), 3.49-3.63 (m, 4H), 2.81-3.02 (m, 4H), 2.24 (s, 3H), 2.16 (s, 3H), 2.11 (s, 3H), 1.43 (d, J=6.57 Hz, 6H); LCMS=513.3 (MH+).

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