Reaktion #172707

Reaktionsgleichung

Water

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

[2-(trifluoromethyl)phenyl]boronic acid

Sodium bicarbonate

→

title compound

Ausbeute 75.1%

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

Ausbeute 75.1%

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 solids that precipitated
4. 4
   Filtrationwere filtered off
5. 5
   workup.ADDITIONDCM/MeOH (1:1) was added
6. 6
   Sonstigeit was pre-absorbed on silica gel
7. 7
   Sonstigepurified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH)
8. 8
   SonstigeFractions were evaporated
9. 9
   workup.ADDITIONEtOAc was added along with some hexanes, it
10. 10
    Sonstigewas sonicated
11. 11
    Sonstigethe solids that precipitated
12. 12
    Filtrationwere filtered
13. 13
    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 (100 mg, 0.24 mmol) and [2-(trifluoromethyl)phenyl]boronic acid (68.3 mg, 0.36 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (9.78 mg, 0.012 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (60.4 mg, 0.72 mmol) was added and the insoluble mixture was heated in a microwave at 110° C. for 15 min. Water was added and the solids that precipitated were filtered off. DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added along with some hexanes, it was sonicated and the solids that precipitated were filtered and dried to afford the title compound (87 mg, 74%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) ppm 11.52 (s, 1H) 8.53 (t, J=4.80 Hz, 1H) 8.43 (s, 1H) 7.88 (d, J=7.83 Hz, 1H) 7.81 (s, 1H) 7.77 (t, J=7.45 Hz, 1H) 7.66 (t, J=7.71 Hz, 1H) 7.53-7.57 (m, 2H) 5.87 (s, 1H) 5.05 (dt, J=13.14, 6.57 Hz, 1H) 4.35 (d, J=4.80 Hz, 2H) 2.19 (s, 3H) 2.10 (s, 3H) 1.48 (s, 3H) 1.47 (s, 3H). MS(ES) [M+H]+ 483.0.

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