Dimethylformamide → HCID 178522861, compound

HRID 2289990Notes

Reaction equation

HRID 2289990 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([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](I)=[CH:17][CH:16]=3)=[O:11])=[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:7]=[CH:6][C:5]([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]([C:31]#[C:30][CH2:29][OH:32])=[CH:17][CH:16]=3)=[O:11])=[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 Example 40 (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 concentrateed to obtain a brown residue. The residue was placed under high vac to remove residual DMF. The residue was adsorbed onto silica and chromatographed eluting with 2% MeOH in CH2Cl2 and 3% MeOH in CH2Cl2. Fractions homogenous by TLC were 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. concentrationThe reaction mixture is concentrated
  2. customto remove Et2NH
  3. customThe resulting residue is partitioned between CH2Cl2 (3×) and H2O
  4. customA brown solid precipitated from the CH2Cl2 layer
  5. filtrationis filtered
  6. customcollected
  7. customto obtain pure product
  8. dry with materialdried over Na2SO4
  9. customto obtain a brown residue
  10. customto remove residual DMF
  11. customchromatographed
  12. washeluting with 2% MeOH in CH2Cl2 and 3% MeOH in CH2Cl2
  13. customcondensed
  14. customrecrystallized with EtOAc/hexanes
  15. customto obtain a creme solid

Sources & evidence

ORD record
ord-1f083413d5784d5b92544388520721dd
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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