Reaktion #88365

Reaktionsgleichung

acetic acid

Propane-1-sulfonic acid {3-[5-bromo-1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

propane-1-sulfonic acid {3-[5-bromo-1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

1H-indole-5-boronic acid

potassium carbonate

→

desired compound

propane-1-sulfonic acid {3-[1-(2,6-dichloro-benzoyl)-5-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

Lösungsmittel

tetrahydrofuran

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe organic layer is washed with brine
2. 2
   Trocknendried over magnesium sulfate
3. 3
   Filtrationfiltered
4. 4
   Einengenthe filtrate concentrated under vacuum
5. 5
   workup.DISSOLUTIONThe resulting material is dissolved in 1 mL of dimethylformamide
6. 6
   Sonstigepurified by HPLC
7. 7
   Wascheneluting with water/acetonitrile and 0.1% trifluoroacetic acid, 40-85% acetonitrile at 15 mL per minute
8. 8
   Einengenconcentrated under vacuum

Vorschrift

Propane-1-sulfonic acid {3-[5-bromo-1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide (11, 113 mg, 0.18 mmol) and 1H-indole-5-boronic acid (14, 44 mg, 0.27 mmol) are dissolved in 4 mL of tetrahydrofuran, then 2 mL of 1M aqueous potassium carbonate and 1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (6.5 mg, 0.018 mmol, 10%) are added. The reaction mixture is heated at 70° C. overnight. The reaction is neutralized with acetic acid and diluted with ethyl acetate and water. The organic layer is washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is dissolved in 1 mL of dimethylformamide and purified by HPLC using a C8 column, eluting with water/acetonitrile and 0.1% trifluoroacetic acid, 40-85% acetonitrile at 15 mL per minute. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound. MS (ESI)=[M+H+]+=669.5. This compound is a prodrug of P-0012, or can be further reacted to remove the dichlorobenzoyl protecting group to provide P-0012.

Quelle