Cesium carbonate → (R)-2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropoxy)-6-fluoroquinoline

HRID 876498Notes

Reaction equation

HRID 876498 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([OH:21])[CH:14]=[C:15]([F:20])[CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.CS(O[CH2:27][C:28]([C@@H:31]1[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[O:32]1)([CH3:30])[CH3:29])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:21][CH2:30][C:28]([C@@H:31]4[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[O:32]4)([CH3:27])[CH3:29])[CH:14]=[C:15]([F:20])[CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 86654366(R)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropyl methanesulfonateHCID 1363378052-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol

Product 1

HCID 67234098(R)-2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropoxy)-6-fluoroquinolineYield 134.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol (0.09 g, 0.34 mmol), (R)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropyl methanesulfonate (0.11 g, 0.45 mmol) and cesium carbonate (0.22 g, 0.69 mmol) were added to 1 to 2 mL of DMA and heated to 85° C. for 4-5 hours. The reaction was concentrated and treated with water and ethyl acetate. The reaction was extracted several times with ethyl acetate. The organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified on Silica gel using 2% NH4OH in isopropyl acetate and DCM to provide 200 mgs of the desired product (85% pure).

Workup

  1. concentrationThe reaction was concentrated
  2. additiontreated with water and ethyl acetate
  3. extractionThe reaction was extracted several times with ethyl acetate
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on Silica gel using 2% NH4OH in isopropyl acetate and DCM

Sources & evidence

ORD record
ord-b4adb603c10a4a6db88ba8f9723a729e
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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