Sodium hydride → HCID 16073827, compound

HRID 1067959Notes

Reaction equation

HRID 1067959 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:27]=[CH:26][C:7]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18]([CH2:23][OH:24])=[CH:17][C:16]=3[F:25])=[O:11])=[CH:6][CH:5]=1.Br[CH2:29][CH2:30][CH2:31][O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[C:16]([F:25])[CH:17]=[C:18]([CH2:23][OH:24])[CH:19]=3)[N:14]([CH2:29][CH2:30][CH2:31][O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)[CH:13]=2)=[O:11])=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyranHCID 178522915HCID 178522915, compound

Product 1

HCID 16073827HCID 16073827, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (60% dispersion in oil, 11.1 mg) in 2.5 mL anhydrous DMF is added N-(4-chlorobenzyl)-8-fluoro-4-hydroxy-6-(hydroxymethyl)-3-quinolinecarboxamide from Preparation No. 7 (100 mg). After stirring the reaction mixture at room temperature for 15-20 min., 2-(3-bromopropoxy)tetrahydro-2H-pyran (89.4 mg) is added. The reaction is stirred at room temperature for 3 days. The reaction mixture is treated with saturated aqueous NaHCO3, then extracted with CH2Cl2 (3×). The combined organic layers are washed with 15% K2CO3 and H2O (2×), dried over Na2SO4, and condensed to obtain a yellow residue. The residue is chromatographed eluting with 2% MeOH in CH2Cl2. Fractions homogenous by TLC are combined and condensed to afford 34.0 mg (24%) of the title compound as a white solid.

Workup

  1. customfrom Preparation No
  2. stirringThe reaction is stirred at room temperature for 3 days
  3. extractionextracted with CH2Cl2 (3×)
  4. washThe combined organic layers are washed with 15% K2CO3 and H2O (2×)
  5. dry with materialdried over Na2SO4, and condensed
  6. customto obtain a yellow residue
  7. customThe residue is chromatographed
  8. washeluting with 2% MeOH in CH2Cl2
  9. customcondensed

Sources & evidence

ORD record
ord-6591cda105af4dca956772c965ebff53
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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