Phosphorus oxychloride → 2-Hydroxy-8-[(4-isopropyl-1,3-thiazol-2-yl)methoxy]-4-oxo-4 H-pyrido[1,2-a]-pyrimidine-3-carbaldehyde

HRID 1828431Notes

Reaction equation

HRID 1828431 reaction equation
P(Cl)(Cl)(Cl)=O.[OH:6][C:7]1[N:8]=[C:9]2[CH:17]=[C:16]([O:18][CH2:19][C:20]3[S:21][CH:22]=[C:23]([CH:25]([CH3:27])[CH3:26])[N:24]=3)[CH:15]=[CH:14][N:10]2[C:11](=[O:13])[CH:12]=1.[C:28](=O)([O-])[OH:29].[Na+]>CN(C)C=O>[OH:6][C:7]1[N:8]=[C:9]2[CH:17]=[C:16]([O:18][CH2:19][C:20]3[S:21][CH:22]=[C:23]([CH:25]([CH3:27])[CH3:26])[N:24]=3)[CH:15]=[CH:14][N:10]2[C:11](=[O:13])[C:12]=1[CH:28]=[O:29]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1357244322-Hydroxy-8-[(4-isopropyl-1,3-thiazol-2-yl)methoxy]-4H-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 1357244292-Hydroxy-8-[(4-isopropyl-1,3-thiazol-2-yl)methoxy]-4-oxo-4 H-pyrido[1,2-a]-pyrimidine-3-carbaldehydeYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Dimethylformamide (3 ml) was added with phosphorus oxychloride (130 μl, 1.42 mmol) under ice cooling, and further added dropwise with 2-hydroxy-8-[(4-isopropyl-1,3-thiazol-2-yl)methoxy]-4H-pyrido[1,2-a]pyrimidin-4-one (300 mg, 0.945 mmol) dissolved in dimethylformamide (6 ml) under ice cooling. Then, the reaction solution was returned to room temperature and stirred for 1 hour. The reaction was stopped with saturated aqueous sodium hydrogencarbonate, and the reaction solution was extracted with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform→chloroform:methanol=50:1→30:1→10:1) to obtain 45 mg (14%) of the title compound.

Workup

  1. customwas returned to room temperature
  2. extractionthe reaction solution was extracted with chloroform
  3. washThe resulting organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (chloroform→chloroform:methanol=50:1→30:1→10:1)

Sources & evidence

ORD record
ord-e5e681c83cc34557898d3b16f2a4bfda
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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