Cesium carbonate → [6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-cyclopropanecarbonyl-piperazin-1-yl)-methanone

HRID 1786476Notes

Reaction equation

HRID 1786476 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[O:12])[NH:8]2)=[CH:4][C:3]=1[O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([N:13]3[CH2:18][CH2:17][N:16]([C:38]([CH:35]4[CH2:37][CH2:36]4)=[O:39])[CH2:15][CH2:14]3)=[O:12])[NH:8]2)=[CH:4][C:3]=1[O:19][CH:20]1[CH2:21][CH2:22][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 77637Cyclopropanecarbonyl chlorideHCID 68565620[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone

Product 1

HCID 68573657[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-cyclopropanecarbonyl-piperazin-1-yl)-methanoneYield 46%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of [6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone (example 36, 150 mg, 1.0 eq.) and cesium carbonate (243 mg, 2.0 eq.) in acetonitrile (8 mL) was added cyclopropane carbonylchloride. The reaction mixture was refluxed 4 h. The reaction mixture was concentrated in vacuo and the residue partitioned between tert-butylmethylether and water. The aqueous layer was extracted with tert-butylmethylether and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. The residue was purified by flash chromatography on silica gel with a 98:2 to 95:5:0.25 gradient of dichloromethane/methanol/ammonia as eluant, to afford 59 mg (46%) of the title compound as a light-yellow solid.

Workup

  1. temperatureThe reaction mixture was refluxed 4 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue partitioned between tert-butylmethylether and water
  4. extractionThe aqueous layer was extracted with tert-butylmethylether
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel with a 98:2 to 95:5:0.25 gradient of dichloromethane/methanol/ammonia as eluant

Sources & evidence

ORD record
ord-74d069b74f2c4196b99f3e8b80128187
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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