반응 #90579

반응 방정식

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

용매

water

반응 조건

후처리

1. 1
   기타degassed under N2 for 15 min. (emulsion)
2. 2
   기타degassed for 2 min
3. 3
   기타The reaction flask was sealed
4. 4
   온도the contents heated
5. 5
   온도at reflux for 2 h
6. 6
   여과The suspension was filtered
7. 7
   기타dioxane was removed in vacuo
8. 8
   기타The resultant oil was partitioned between 300 mL of ethyl acetate and 100 mL of water
9. 9
   기타the layers were separated
10. 10
    workup.ADDITIONDecolorizing carbon was added
11. 11
    여과the organic layer was filtered through short pad of silica
12. 12
    workup.ADDITION300 mL of 1 M HCl was added
13. 13
    추출The contents were extracted with ethyl acetate
14. 14
    기타The organic layer was separated
15. 15
    세척washed with brine
16. 16
    건조dried over MgSO4
17. 17
    여과filtered
18. 18
    농축concentrated in vacuo
19. 19
    여과filtered

실험 절차

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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