1H-Indazole-4-boronic acid → HCID 86691498, compound

HRID 2410260Notes

Reaction equation

HRID 2410260 reaction equation
Cl[C:2]1[CH:7]=[C:6]([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]=[CH:4][N:3]=1.[NH:31]1[C:39]2[C:34](=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=2)[CH:33]=[N:32]1>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](=[C:35]([C:2]3[CH:7]=[C:6]([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]=[CH:4][N:3]=3)[CH:36]=[CH:37][CH:38]=2)[CH:33]=[N:32]1

Participants

5

Reactant 2

HCID 441183101H-Indazole-4-boronic acidHCID 86691499HCID 86691499, compound

Product 1

HCID 86691498HCID 86691498, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Tetraisopropyl (2-(2-chloropyridin-4-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate) (78 mg; 0.16 mmol), Pd(PPh3)4 (37 mg; 0.032 mmol) and (1H-indazol-4-yl)boronic acid (52 mg; 0.32 mmol) are mixed in microwave vial (2-5 mL). The vial is capped with a septum, 2.0 mL of DME is added and the reaction mixture is immediately flushed with argon. Sodium carbonate solution (0.20 mL; 2M) is added and the mixture is flushed again with argon. The vial is re-capped with Teflon cap and irradiated in microwave for 15 min at 110° C. The mixture is cooled, diluted with EtOAc and filtered through Celite™, the Celite™ is rinsed 3× with EtOAc/MeOH (1:1). The filtrates are concentrated and deposited on silica. Purification by column chromatography on silica gel (pre treated with 1% NEt3 in hexanes) using a solvent gradient from hexanes to EtOAc, and then to 50% MeOH in EtOAc lead to the isolation of the product as a yellow oil (28 mg; 31% yield).

Workup

  1. additionis added
  2. customthe reaction mixture is immediately flushed with argon
  3. additionSodium carbonate solution (0.20 mL; 2M) is added
  4. customthe mixture is flushed again with argon
  5. customThe vial is re-capped with Teflon
  6. customcap
  7. customirradiated in microwave for 15 min at 110° C
  8. temperatureThe mixture is cooled
  9. additiondiluted with EtOAc
  10. filtrationfiltered through Celite™
  11. washthe Celite™ is rinsed 3× with EtOAc/MeOH (1:1)
  12. concentrationThe filtrates are concentrated
  13. customPurification by column chromatography on silica gel (pre treated with 1% NEt3 in hexanes)

Sources & evidence

ORD record
ord-59cf6cbbab5f4f02800700d103147657
Source dataset
uspto-grants-2014_08
Patent number
US08816082B2

Reaction notes

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