Cesium carbonate → (1,1-Dioxo-thiomorpholin-4-yl)-[1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

HRID 493987Notes

Reaction equation

HRID 493987 reaction equation
[O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[CH:30](CS([O-])(=O)=O)([CH3:32])[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[O:29]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH:30]([CH3:32])[CH3:31])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 16739577(1,1-Dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanoneHCID 22141912Isopropyl-methanesulfonate

Product 1

HCID 16739606(1,1-Dioxo-thiomorpholin-4-yl)-[1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanoneYield 47.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To a mixture of (1,1-dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (Example 2, 100 mg, 1.0 eq.) and isopropyl-methanesulfonate (67 mg, 2.0 eq.) in dimethylformamide (4 mL) was added cesium carbonate (156 mg, 2.0 eq.). The solution was stirred 22 h at 95° C. The reaction mixture was concentrated in vacuo and the residue partitioned between water and methyl-tert-butylether. The aqueous layer was extracted with methyl-tert-butylether. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo and then purified on silica, eluting with cyclohexane/ethyl acetate. One fraction was isolated and dried in vacuo, to yield 52 mg (47%) of the desired product as off-white solid. MS (m/e): 462.5 (MH+, 100%)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between water and methyl-tert-butylether
  3. extractionThe aqueous layer was extracted with methyl-tert-butylether
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified on silica
  9. washeluting with cyclohexane/ethyl acetate
  10. customOne fraction was isolated
  11. customdried in vacuo

Sources & evidence

ORD record
ord-eda866f5f62647fe89f0a903dfa58cd2
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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