Lithium Hydroxide → (S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide
Reaction equation
[CH3:1][O:2][C@@H:3]([CH3:7])[C:4](O)=[O:5].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C.[Br:30][C:31]1[C:32]([F:41])=[C:33]2[C:39]([NH2:40])=[CH:38][NH:37][C:34]2=[N:35][CH:36]=1.[Li+].[OH-].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Br:30][C:31]1[C:32]([F:41])=[C:33]2[C:39]([NH:40][C:4](=[O:5])[C@@H:3]([O:2][CH3:1])[CH3:7])=[CH:38][NH:37][C:34]2=[N:35][CH:36]=1Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Procedure
(S)-2-Methoxypropanoic acid (181 mg, 1.74 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (443 mg, 1.74 mmol) and triethylamine (440 mg, 4.35 mmol) were added to 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.87 mmol, Example 1, Step H) in DCM (50 mL). The reaction was stirred at room temperature for 1 hour, and then 3M aqueous LiOH (4 mL) was added. The reaction was stirred for 1 hour, and then saturated aqueous Na2CO3 was added (200 mL). The aqueous phase was extracted 3 times with DCM (200 mL), and then the combined organic phases were dried over MgSO4 and concentrated to dryness. The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 20-100% CH3CN/water gradient; 20 CV) to yield (S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (131 mg, 48% yield) as a solid.
Workup
- stirringThe reaction was stirred for 1 hour
- extractionThe aqueous phase was extracted 3 times with DCM (200 mL)
- dry with materialthe combined organic phases were dried over MgSO4
- concentrationconcentrated to dryness
- customThe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
Sources & evidence
- ORD record
- ord-e36b0adb6a1141169a1b9a50e89e4464
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178131B2
Reaction notes
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