Cesium carbonate → HCID 86273582, compound

HRID 1497733Notes

Reaction equation

HRID 1497733 reaction equation
[CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:18]1[N:35]=[CH:34][C:21]2[NH:22][C:23](=[O:33])[N:24]([CH3:32])[CH:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]=2[CH:19]=1>>[CH3:1][C:2]1[C:6]([C:18]2[N:35]=[CH:34][C:21]3[NH:22][C:23](=[O:33])[N:24]([CH3:32])[CH:25]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:20]=3[CH:19]=2)=[C:5]([CH3:10])[O:4][N:3]=1

Participants

4

Reactant 3

HCID 10796Cesium carbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 117600654HCID 117600654, compound

Product 1

HCID 86273582HCID 86273582, compound

Conditions

Temperature
90 °C

Procedure

3,5-dimethylisoxazole-4-boronic acid (140 mg, 0.993 mmol), cesium carbonate (500 mg, 1.519 mmol) and 1,1-bis(diphenylphosphino)ferocene-palladium(II)dichloride dichloromethane complex are added to a microwave vessel flushed with argon. Dimethyl sulfoxide (5 mL) is added and the mixture purged with argon. Finally, 6-Chloro-3-methyl-4-phenyl-3,4-dihydro-1H-pyrido[3,4-d]pyrimidin-2-one (140 mg, 0.511 mmol) is added and the mixture again purged with argon and heated in a microwave oven at 90° C. for 120 minutes. The mixture is poured onto water and the aqueous phase extracted with dichloromethane. The organic phase is dried over magnesium sulfate. The drying agent is removed by filtration. The filtrate is concentrated to dryness and purified by chromatography on silica gel using a dichloromethane/methanol gradient. The product fractions are evaporated to dryness and purified by reverse phase HPLC. This affordes the desired product as a white solid.

Workup

  1. customflushed with argon
  2. additionDimethyl sulfoxide (5 mL) is added
  3. customthe mixture purged with argon
  4. customthe mixture again purged with argon
  5. additionThe mixture is poured onto water
  6. extractionthe aqueous phase extracted with dichloromethane
  7. dry with materialThe organic phase is dried over magnesium sulfate
  8. customThe drying agent is removed by filtration
  9. concentrationThe filtrate is concentrated to dryness
  10. custompurified by chromatography on silica gel using a dichloromethane/methanol gradient
  11. customThe product fractions are evaporated to dryness
  12. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-78d570b3ce754f47bc687ce93fc76238
Source dataset
uspto-grants-2015_12
Patent number
US09199988B2

Reaction notes

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