Boron tribromide → HCID 24782416, compound

HRID 549534Notes

Reaction equation

HRID 549534 reaction equation
[NH2:1][C:2](=[O:45])[CH2:3][N:4]([CH3:44])[C:5](=[O:43])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N:12]2[C:20]3[C:15](=[C:16]([NH:22][CH2:23][C:24]([OH:42])([C:38]([F:41])([F:40])[F:39])[CH2:25][C:26]([C:29]4[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=4[O:36]C)([CH3:28])[CH3:27])[CH:17]=[C:18]([CH3:21])[CH:19]=3)[CH:14]=[N:13]2)[CH:7]=1.C(=O)=O.CC(C)=O.B(Br)(Br)Br>ClCCl>[NH2:1][C:2](=[O:45])[CH2:3][N:4]([CH3:44])[C:5](=[O:43])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N:12]2[C:20]3[C:15](=[C:16]([NH:22][CH2:23][C:24]([OH:42])([C:38]([F:39])([F:40])[F:41])[CH2:25][C:26]([C:29]4[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=4[OH:36])([CH3:28])[CH3:27])[CH:17]=[C:18]([CH3:21])[CH:19]=3)[CH:14]=[N:13]2)[CH:7]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 18522661Acetone cardiceHCID 24782158HCID 24782158, compound

Product 1

HCID 24782416HCID 24782416, compoundYield 31.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(2-Amino-2-oxoethyl)-3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)-N-methylbenzamide (55.1 mg, 0.0875 mmol) was dissolved in anhydrous dichloromethane (0.2 mL) and cooled to −78° C. (cardice/acetone bath) under nitrogen. Boron tribromide (1.0M in dichloromethane) (0.435 mL, 0.435 mmol) was then added portionwise and after 5 minutes the mixture was allowed to warm to room temperature. The reaction was stirred at room temperature for 6 hours, re-cooled to −78° C. and quenched with methanol (1 mL). The reaction was warmed to room temperature when more dichloromethane (1 mL) and aqueous saturated sodium hydrogen carbonate solution (2 mL) were added and the mixture stirred vigorously and then poured onto a hydrophobic frit and the dichloromethane layer collected and evaporated in vacuo. This crude product was purified by mass-directed autopreparation (System B). Product containing fractions were combined and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was re-extracted twice more with dichloromethane and the combined organic extracts were washed successively water and brine, dried through a hydrophobic frit and evaporated in vacuo to give the title compound (17.2 mg).

Workup

  1. temperaturere-cooled to −78° C.
  2. customquenched with methanol (1 mL)
  3. temperatureThe reaction was warmed to room temperature when more dichloromethane (1 mL) and aqueous saturated sodium hydrogen carbonate solution (2 mL)
  4. additionwere added
  5. stirringthe mixture stirred vigorously
  6. additionpoured onto a hydrophobic frit
  7. customthe dichloromethane layer collected
  8. customevaporated in vacuo
  9. customThis crude product was purified by mass-directed autopreparation (System B)
  10. additionProduct containing fractions
  11. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  12. extractionThe aqueous layer was re-extracted twice more with dichloromethane
  13. washthe combined organic extracts were washed successively water and brine
  14. customdried through a hydrophobic frit
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-29757964746340ce885f46157c608dd0
Source dataset
uspto-grants-2011_05
Patent number
US07943651B2

Reaction notes

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