Reaction #67135

Reaction equation

2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine

tripotassium phosphate monohydrate

2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine

6-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole

→

title compound

Yield 43.6%

5-{4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methyl phenyl)sulfonyl]-1H-indazol-6-yl}-2-(methyloxy)-3-pyridinamine

Yield 43.6%

Solvents

water

1,4-dioxane

Conditions

Workup

1. 1
   Temperaturethe reaction mixture heated at 80° C. for a further 18 h
2. 2
   OtherThe solvent was removed in vacuo
3. 3
   Otherthe residue partitioned between DCM (50 ml) and water (50 ml)
4. 4
   OtherThe layers were separated (hydrophobic frit)
5. 5
   Concentrationthe organic concentrated in vacuo
6. 6
   Otherthe residue purified by column chromatography, loading in dichloromethane
7. 7
   Otherpurified on a silica cartridge (100 g)
8. 8
   Otherover 40 mins
9. 9
   Concentrationconcentrated in vacuo to a brown gum
10. 10
    OtherThis was purified again by column chromatography, loading in dichloromethane
11. 11
    Otherpurified on a silica cartridge (50 g)
12. 12
    Otherover 40 mins
13. 13
    Otherevaporated in vacuo

Procedure

6-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole (680 mg, 1.244 mmol) was dissolved in 1,4-dioxane (15 ml) and water (1.5 ml). 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (311 mg, 1.244 mmol), bis(diphenylphosphino)ferrocene palladium dichloride (182 mg, 0.249 mmol) and tripotassium phosphate monohydrate (860 mg, 3.73 mmol) were added and the reaction mixture heated at 80° C. for 2 h. 2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (0.1 eq, 31 mg) was added and the reaction mixture heated at 80° C. for a further 18 h. The solvent was removed in vacuo and the residue partitioned between DCM (50 ml) and water (50 ml). The layers were separated (hydrophobic frit), the organic concentrated in vacuo and the residue purified by column chromatography, loading in dichloromethane and purified on a silica cartridge (100 g), using a 0-30% methanol(+1% triethylamine)-dichloromethane over 40 mins. The appropriate fractions were combined and concentrated in vacuo to a brown gum. This was purified again by column chromatography, loading in dichloromethane and purified on a silica cartridge (50 g) using a 0-100% ethyl acetate-cyclohexane+0-20% methanol over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (320 mg).

Source