Water → HCID 66823762, compound

HRID 1748122Notes

Reaction equation

HRID 1748122 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[C:21]4=[N:22][S:23](=[O:27])(=[O:26])[CH2:24][CH2:25][N:20]4[CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)[CH:9]=[CH:8]1.Br[CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1.O>CS(C)=O.CCOC(C)=O>[F:37][C:34]1[CH:35]=[CH:36][C:31]([CH2:30][CH2:29][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]4[C:21]5=[N:22][S:23](=[O:27])(=[O:26])[CH2:24][CH2:25][N:20]5[CH2:19][CH2:18][CH2:17]4)=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 5731534-Fluorophenethyl bromideHCID 66749795HCID 66749795, compound

Product 1

HCID 66823762HCID 66823762, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of cesium carbonate (435 mg) and 9-(1H-indol-5-yl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (200 mg) in DMSO (5 ml) was added 1-(2-bromoethyl)-4-fluorobenzene (136 mg). The mixture was stirred at room temperature for 1 day. Water and EtOAc were added and the extracted organic layer was washed with brine, dried over anhydrous sodium sulfate. Silica-gel was added to the organic layer and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with MeOH in EtOAc), concentrated and dissolved in THF (dry) (25 mL) and MeOH (25 mL). Then platinum(IV) oxide (46 mg) was added and the mixture was stirred at room temperature under hydrogen overnight. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). The filtrate was concentrated and the residue was purified by column chromatography (1st: NH silica gel, eluted with MeOH in EtOAc, 2nd: silica gel, eluted with EtOAc) to give the title compound (5.7 mg) as a white solid.

Workup

  1. washthe extracted organic layer was washed with brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. additionSilica-gel was added to the organic layer
  4. customthe volatiles were removed in vacuo
  5. customwas purified by column chromatography (silica gel, eluted with MeOH in EtOAc)
  6. concentrationconcentrated
  7. dissolutiondissolved in THF (dry) (25 mL)
  8. additionThen platinum(IV) oxide (46 mg) was added
  9. stirringthe mixture was stirred at room temperature under hydrogen overnight
  10. additionActivated carbon was added
  11. customthe insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc)
  12. concentrationThe filtrate was concentrated
  13. customthe residue was purified by column chromatography (1st: NH silica gel, eluted with MeOH in EtOAc, 2nd: silica gel, eluted with EtOAc)

Sources & evidence

ORD record
ord-263e8119034c44d7acb062f352ea5d44
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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