Potassium Carbonate → tetraisopropyl(2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

HRID 2410256Notes

Reaction equation

HRID 2410256 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([P:21](=[O:30])([O:26][CH:27]([CH3:29])[CH3:28])[O:22][CH:23]([CH3:25])[CH3:24])([P:11](=[O:20])([O:16][CH:17]([CH3:19])[CH3:18])[O:12][CH:13]([CH3:15])[CH3:14])[F:10])[CH:5]=[N:6][CH:7]=1.[NH:31]1[C:39]2[C:34](=[CH:35][C:36](B(O)O)=[CH:37][CH:38]=2)[CH:33]=[N:32]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[NH:31]1[C:39]2[C:34](=[CH:35][C:36]([C:2]3[CH:3]=[C:4]([CH2:8][C:9]([P:11](=[O:20])([O:16][CH:17]([CH3:19])[CH3:18])[O:12][CH:13]([CH3:14])[CH3:15])([P:21](=[O:30])([O:22][CH:23]([CH3:25])[CH3:24])[O:26][CH:27]([CH3:29])[CH3:28])[F:10])[CH:5]=[N:6][CH:7]=3)=[CH:37][CH:38]=2)[CH:33]=[N:32]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 177505041H-Indazole-5-boronic acidHCID 86691496Tetraisopropyl(2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

Product 1

HCID 86691495tetraisopropyl(2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)Yield 45%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Tetraisopropyl (2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate) (85 mg; 0.16 mmol), Pd(PPh3)4 (36.9 mg; 0.032 mmol) and (1H-indazol-5-yl)boronic acid (39 mg; 0.24 mmol) are added to the vial and the vial is capped with a septum. DME (4 mL) is added and the vial is flushed with argon, an aqueous solution of potassium carbonate (2.5 eq.) is added and the mixture is flushed again with argon. The reaction mixture is stirred at 80° C. for 36 h under an atmosphere of argon. The mixture was cooled to RT, diluted with EtOAc and filtered through Celite™, the Celite™ is washed three times with EtOAc/MeOH (1:1). The filtrate is deposited on silica gel and purified by column chromatography (on pre washed silica with 1% NEt3 in hexanes) using a solvent gradient from hexanes to EtOAc and then to 50% MeOH in EtOAc. The pure product is isolated as a brown oil (41 mg, 45% yield).

Workup

  1. customis capped with a septum
  2. customthe vial is flushed with argon
  3. customthe mixture is flushed again with argon
  4. temperatureThe mixture was cooled to RT
  5. additiondiluted with EtOAc
  6. filtrationfiltered through Celite™
  7. washthe Celite™ is washed three times with EtOAc/MeOH (1:1)
  8. custompurified by column chromatography (on pre washed silica with 1% NEt3 in hexanes)

Sources & evidence

ORD record
ord-71ba16d3ec9e42a0bb8259ab96059151
Source dataset
uspto-grants-2014_08
Patent number
US08816082B2

Reaction notes

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