Sodium hydride → HCID 16226478, compound

HRID 559211Notes

Reaction equation

HRID 559211 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:26](=[O:27])[N:25]([CH3:28])[C:11]3[N:12]([CH3:24])[C:13]4[C:18]([C:10]=3[CH:9]=2)=[CH:17][C:16]([C:19]2[CH:23]=[CH:22][NH:21][N:20]=2)=[CH:15][CH:14]=4)=[CH:4][CH:3]=1.[H-].[Na+].C1OCCOC2C(=CC=CC=2)OCCOCCOC2[C:34](=CC=CC=2)[O:33][CH2:32]1.COCBr.C([O-])(O)=O.[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:26](=[O:27])[N:25]([CH3:28])[C:11]3[N:12]([CH3:24])[C:13]4[C:18]([C:10]=3[CH:9]=2)=[CH:17][C:16]([C:19]2[CH:23]=[CH:22][N:21]([CH2:32][O:33][CH3:34])[N:20]=2)=[CH:15][CH:14]=4)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 26541Dibenzo-18-crown-6HCID 83093Bromomethyl methyl etherHCID 516892Sodium BicarbonateHCID 178481370HCID 178481370, compound

Product 1

HCID 16226478HCID 16226478, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

303 mg (0.81 mmol) of compound B 3-(4-fluorophenyl)-1,9-dimethyl-6-(1H-pyrazol-3-yl)-1,9-dihydropyrido[2,3-b]indol-2-one are dissolved in 8 ml of DMF. 50 mg (1.22 mmol) of 60% NaH and a spatula of dibenzo-18-crown-6 are added. After stirring for 5 minutes, 73 μl (0.89 mmol) of bromomethyl methyl ether are added. The mixture is left to stir for 4 h at ambient temperature. A saturated NaHCO3 solution is added, the mixture extracted with EtOAc, and the organic phase is dried over MgSO4, filtered, and concentrated to dryness, adsorbing onto silica. The mixture is enriched in beta isomer by chromatography on a silica column, elution being carried out with 70/30 EtOAc/cyclohexane (ratio obtained: 62/38 beta/alpha) and then by means of a second purification by chromatography on a silica column, elution being carried out with 60/40 EtOAc/cyclohexane.

Workup

  1. waitThe mixture is left
  2. stirringto stir for 4 h at ambient temperature
  3. extractionthe mixture extracted with EtOAc
  4. dry with materialthe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. washThe mixture is enriched in beta isomer by chromatography on a silica column, elution
  8. customby means of a second purification by chromatography
  9. washon a silica column, elution

Sources & evidence

ORD record
ord-bf4cbe26699f415d9d5bd254fce23443
Source dataset
uspto-grants-2011_11
Patent number
US08063061B2

Reaction notes

Loading…