Reaktion #90578

Reaktionsgleichung

sodium carbonate

6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine

→

title compound

N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide

Lösungsmittel

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe contents were degassed with argon for 30 min
2. 2
   Sonstigethe contents again degassed with argon for 10 min
3. 3
   Temperaturat reflux for 3 h
4. 4
   workup.ADDITIONThe reaction mixture was diluted with water (100 mL)
5. 5
   Extraktionextracted with ethyl acetate (3×150 mL)
6. 6
   TrocknenThe combined organic layers were dried over anhydrous Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated
9. 9
   Sonstigeto afford the crude product (2.8 g)
10. 10
    SonstigeThe crude compound was purified by column chromatography over silica gel (100-200 mesh, eluent: 0-10% MeOH: DCM)
11. 11
    Sonstigethe obtained product was further triturated with diethyl ether (100 mL)

Vorschrift

To a stirred solution of 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (2 g, 4.65 mmol) in DMF (100 mL) was added 1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (1.55 g, 5.12 mmol) followed by a solution of sodium carbonate (1.23 g, 11.62 mmol) in water (10 mL) and the contents were degassed with argon for 30 min. After that PdCl2(PPh3)2(326 mg, 0.464 mmol) was added and the contents again degassed with argon for 10 min. The reaction mixture was stirred at reflux for 3 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated to afford the crude product (2.8 g). The crude compound was purified by column chromatography over silica gel (100-200 mesh, eluent: 0-10% MeOH: DCM), and the obtained product was further triturated with diethyl ether (100 mL) to afford the title compound as an off white solid (1.2 g, 50%). 1H NMR (DMSO-d6 400 MHz): δ 1.493 (d, J=6.4 Hz, 6H), 2.092 (s, 3H), 2.286 (s, 3H), 2.409 (s, 3H), 2.424 (s, 3H), 2.632 (s, 4H), 3.621 (s, 4H), 4.603-4.685 (m, 3H), 5.880 (s, 1H), 6.606 (d, J=8.8 Hz, 1H), 7.016 (s, 1H), 7.261 (s, 1H), 7.433 (s, 1H), 7.675-7.704 (dd, J=9 Hz, 2.4 Hz, 1H), 8.425 (d, J=2.0 Hz, 1H), 11.699 (brs, 1H); LCMS (ES+): 525.23 [M−H].

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