Dimethylformamide → HCID 178522861, compound

HRID 1067256Notes

Reaction equation

HRID 1067256 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16](I)=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1.CN(C=O)C.[CH2:29]([OH:32])[C:30]#[CH:31]>N(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([C:31]#[C:30][CH2:29][OH:32])=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 7859Propargyl alcoholHCID 178522879HCID 178522879, compound

Product 1

HCID 178522861HCID 178522861, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

To a mixture of N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-quinolinecarboxamide from Preparation No. 1 (0.494 g) in Et2NH (12.9 mL) is added CuI (10.8 mg) and (Ph3P)2PdCl2 (39.7 mg). DMF (2 mL) is added to solubilize the reactants. To this solution is added propargyl alcohol (0.066 mL) and the reaction is stirred at room temperature for 2 days. The reaction mixture is concentrated to remove Et2NH. The resulting residue is partitioned between CH2Cl2 (3×) and H2O. A brown solid precipitated from the CH2Cl2 layer is filtered and collected to obtain pure product as indicated by NMR. The organic layers are combined, dried over Na2SO4, and concentrated to obtain a brown residue. The residue is placed under high vac to remove residual DMF. The residue is adsorbed onto silica and chromatographed eluting with 2% MeOH in CH2Cl2 and 3% MeOH in CH2Cl2. Fractions homogenous by TLC are combined, condensed and recrystallized with EtOAc/hexanes to obtain a creme solid. The two crops yielded 325.4 mg (79%) of the desired product as a tan solid.

Workup

  1. customfrom Preparation No
  2. concentrationThe reaction mixture is concentrated
  3. customto remove Et2NH
  4. customThe resulting residue is partitioned between CH2Cl2 (3×) and H2O
  5. customA brown solid precipitated from the CH2Cl2 layer
  6. filtrationis filtered
  7. customcollected
  8. customto obtain pure product
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customto obtain a brown residue
  12. customto remove residual DMF
  13. customchromatographed
  14. washeluting with 2% MeOH in CH2Cl2 and 3% MeOH in CH2Cl2
  15. customcondensed
  16. customrecrystallized with EtOAc/hexanes
  17. customto obtain a creme solid

Sources & evidence

ORD record
ord-e009e66276bf4190ac6323cc0540d844
Source dataset
uspto-grants-2001_06
Patent number
US06248736B1

Reaction notes

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