Reaktion #172609

Reaktionsgleichung

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

1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Sodium bicarbonate

→

title compound

Ausbeute 77.2%

N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-4-carboxamide

Ausbeute 77.2%

Lösungsmittel

dioxane water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIn a 25 mL sealable tube under nitrogen were combined
2. 2
   Sonstigethe resulting mixture was degassed with nitrogen for 10 min
3. 3
   Sonstigethe vessel was sealed
4. 4
   SonstigeThe mixture was evaporated
5. 5
   workup.ADDITIONDCM/MeOH (1:1) was added
6. 6
   Sonstigethe contents pre-absorbed on silica gel
7. 7
   Sonstigepurified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
8. 8
   Sonstigewas sonicated
9. 9
   Sonstigethe solids that precipitated
10. 10
    Filtrationwere filtered
11. 11
    workup.ADDITIONAcetonitrile was added
12. 12
    Sonstigesolids that precipitated
13. 13
    Filtrationwere filtered
14. 14
    Waschenfurther washed with acetonitrile/ether (2:8)
15. 15
    Sonstigedried

Vorschrift

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (110 mg, 0.26 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (82 mg, 0.4 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (10.8 mg, 0.013 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (66.4 mg, 0.79 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 100° C. for 20 min. The mixture was evaporated, DCM/MeOH (1:1) was added, and the contents pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes, it was sonicated, and the solids that precipitated were filtered. Acetonitrile was added, solids that precipitated were filtered, and further washed with acetonitrile/ether (2:8) and dried to afford the title compound as an off-white solid (84 mg, 76%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.48 (t, J=4.93 Hz, 1H) 8.31 (s, 1H) 8.26 (s, 1H) 8.04 (s, 1H) 8.03 (s, 1H) 7.81 (d, J=1.01 Hz, 1H) 5.90 (s, 1H) 5.06 (quin, J=6.57 Hz, 1H) 4.39 (s, 1H) 4.38 (s, 1H) 3.90 (s, 3H) 2.23 (s, 3H) 2.13 (s, 3H) 1.50 (s, 3H) 1.48 (s, 3H); LC-MS (ES) m/z=419.0

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