Triethylamine → HCID 60205526, compound

HRID 408332Notes

Reaction equation

HRID 408332 reaction equation
C([O:4][C:5]([CH3:10])([CH3:9])[C:6](Cl)=[O:7])(=O)C.[Br:11][C:12]1[C:13]([F:22])=[C:14]2[C:20]([NH2:21])=[CH:19][NH:18][C:15]2=[N:16][CH:17]=1.C(N(CC)CC)C>ClCCl>[Br:11][C:12]1[C:13]([F:22])=[C:14]2[C:20]([NH:21][C:6](=[O:7])[C:5]([OH:4])([CH3:9])[CH3:10])=[CH:19][NH:18][C:15]2=[N:16][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205526HCID 60205526, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Chloro-2-methyl-1-oxopropan-2-yl acetate (215 mg, 1.30 mmol) in dry dichloromethane (2 mL) was added dropwise to a solution of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (250 mg, 1.087 mmol; Example 1, Step H) and triethylamine (550 mg, 0.757 mL, 5.43 mmol) in dry dichloromethane (10 mL) cooled on an ice-bath. The resulting solution was stirred at room temperature for 1 hour. The solvent was evaporated. The residue was then stirred in THF (10 mL), treated with an aqueous 2N LiOH solution (3 mL), and stirred at room temperature for 18 hours. The mixture was evaporated under reduced pressure, and the residue dissolved in EtOAc and washed with water (3×20 mL). The organic layer was dried over MgSO4, filtered and concentrated to give N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide (289 mg, 84% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.03 (br s, 1H), 9.27 (s, 1H), 8.36 (d, 1H), 7.69 (d, 1H), 5.84 (s, 1H), 1.37 (s, 6H); LCMS (APCI+) m/z 317.9 (M+H)+, Retention time=2.51 minutes.

Workup

  1. temperaturecooled on an ice-bath
  2. customThe solvent was evaporated
  3. stirringThe residue was then stirred in THF (10 mL)
  4. additiontreated with an aqueous 2N LiOH solution (3 mL)
  5. stirringstirred at room temperature for 18 hours
  6. customThe mixture was evaporated under reduced pressure
  7. dissolutionthe residue dissolved in EtOAc
  8. washwashed with water (3×20 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-245a895fff4f4fe5b50f9bffa8e407ba
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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