Lithium Hydroxide → (S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide

HRID 1923934Notes

Reaction equation

HRID 1923934 reaction equation
[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C([O:16][C@@H:17]([CH3:21])[C:18](O)=[O:19])(=O)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[Li+].[OH-]>C(Cl)Cl.CC#N.O.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:18](=[O:19])[C@@H:17]([OH:16])[CH3:21])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 6326324(2S)-2-(Acetyloxy)propanoic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205672(S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamideYield 9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (0.350 g, 1.52 mmol; Example 1, Step H), (S)-2-acetoxypropanoic acid (0.422 g, 3.20 mmol), BOP-Cl (0.813 g, 3.20 mmol), and triethylamine (1.06 mL, 7.61 mmol) were placed in DCM (5 mL) and stirred for 1 hour. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 1 hour and then poured into water and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-60% CH3CN/water) to give (S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide (0.040 g, 9% yield).

Workup

  1. stirringthe reaction was stirred for 1 hour
  2. extractionextracted with DCM
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product, which
  7. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-16ffd28a8ce546f2bb3ddf44dc479223
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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