6-Hydroxyquinoline → HCID 58710080, compound

HRID 2375824Notes

Reaction equation

HRID 2375824 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[CH:7]2.[Cl-].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]=[C:25]([C:28]2[NH:44][C:31]3[N:32]=[CH:33][N:34]=[C:35]([N+]45CCN(CC4)CC5)[C:30]=3[CH:29]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)(O)[O-].[Na+]>CS(C)=O.C(O)(=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH:24]=[C:25]([C:28]2[NH:44][C:31]3[N:32]=[CH:33][N:34]=[C:35]([O:3][C:4]4[CH:5]=[C:6]5[C:11](=[CH:12][CH:13]=4)[N:10]=[CH:9][CH:8]=[CH:7]5)[C:30]=3[CH:29]=2)[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 113746-HydroxyquinolineHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 69274229HCID 69274229, compound

Product 1

HCID 58710080HCID 58710080, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a stirred suspension of sodium hydride (60% dispersion in mineral oil) (24 mg, 0.6 mmol) in anhydrous DMSO (4 mL) under argon, was added 6-hydroxyquinoline (239 mg, 1.65 mmol). The mixture was allowed to stir at rt for 1 h. To this mixture was added 1-[6-(1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-aza-1-azonia-bicyclo[2.2.2]octane chloride (100 mg, 0.3 mmol) in DMSO (0.3 mL), and the mixture stirred for a further 16 h. TLC analysis showed no starting material so the mixture was neutralised with glacial acetic acid and basified with saturated aqueous sodium bicarbonate solution. The product was extracted in to EtOAc (3×50 mL), the organics dried with MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified on silica gel by elution with iso-hexane:ethyl acetate to yield the title compound. 1H NMR (DMSO, 400 MHz) 1.4 (9H, s), 2.5 (2H, broad), 3.6 (2H, broad), 4.1 (2H, broad), 6.5 (1H, m), 6.7 (1H, s), 7.6 (1H, m), 7.7 (1H, d), 7.9 (1H, s), 8.1 (1H, d), 8.3 (1H, s), 8.4 (1H, d), 8.9 (1H, s), 12.4 (NH, s). MH+=444.24

Workup

  1. stirringthe mixture stirred for a further 16 h
  2. extractionThe product was extracted in to EtOAc (3×50 mL)
  3. dry with materialthe organics dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified on silica gel by elution with iso-hexane

Sources & evidence

ORD record
ord-b4177672908c4e26aec25e7f06336f8f
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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