Water → HCID 68565359, compound

HRID 1786457Notes

Reaction equation

HRID 1786457 reaction equation
[Br: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]([S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[CH2:15][CH2:14]3)=[O:12])[NH:8]2)=[CH:4][C:3]=1[O:24][CH:25]1[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]1.[H-].[Na+].CS(O[CH2:41][C:42]([F:45])([F:44])[F:43])(=O)=O.O>CN(C)C=O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([N:13]3[CH2:14][CH2:15][N:16]([S:19]([CH2:22][CH3:23])(=[O:20])=[O:21])[CH2:17][CH2:18]3)=[O:12])[N:8]2[CH2:41][C:42]([F:45])([F:44])[F:43])=[CH:4][C:3]=1[O:24][CH:25]1[CH2:30][CH2:29][N:28]([CH:31]([CH3:32])[CH3:33])[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5565652,2,2-Trifluoroethyl MethanesulfonateHCID 24958567HCID 24958567, compound

Product 1

HCID 68565359HCID 68565359, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 144 mg (0.26 mmol) [6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4-ethanesulfonyl-piperazin-1-yl)-methanone (example 10) in 3 mL N,N-dimethylformamide, were added 13 mg (0.29 mmol; 55% dispersion in mineral oil) sodium hydride. The reaction mixture was stirred 15 min at 70° C. 68 mg (0.29 mmol) 2,2,2-Trifluoroethyl methanesulfonate were added and the solution was stirred another 2 h at 70° C. After cooling to room temperature, the reaction was poured into water and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant, to afford 86 mg (52%) of the title compound as a light-yellow oil.

Workup

  1. stirringthe solution was stirred another 2 h at 70° C
  2. temperatureAfter cooling to room temperature
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) as eluant

Sources & evidence

ORD record
ord-664e9c5a155c430cac4fb54f62b4950a
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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