Methyl vinyl ketone → HCID 178467735, compound

HRID 2290004Notes

Reaction equation

HRID 2290004 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][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][C:14]=3[F:22])=[O:9])=[CH:4][CH:3]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH:47]([C:49]([CH3:51])=[O:50])=[CH2:48].CCN(CC)CC>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:24]=[CH:23][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](/[CH:48]=[CH:47]/[C:49](=[O:50])[CH3:51])=[CH:15][C:14]=3[F:22])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6570Methyl vinyl ketoneHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 178522917HCID 178522917, compound

Product 1

HCID 178467735HCID 178467735, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(4-chlorobenzyl)-8-fluoro-4-hydroxy-6-iodo-3-quinolinecarboxamide from Example No. 5 (1.0 g), Pd(OAc)2 (9 mg), P(o-tolyl)3 (45.7 mg), methyl vinyl ketone (0.23 mL), and Et3N (0.78 mL) in 5.28 mL anhydrous DMF is heated in a sealed tube at 100° C. overnight. The reaction mixture is cooled to room temperature and then cooled in an ice bath. The cooled reaction mixture is poured into 20 mL ice cold 1N HCl. A brown solid precipitated and is collected. The crude product is adsorbed onto silica and chromatographed eluting with 2% MeOH in CH2Cl2. Fractions homogenous by TLC are combined and condensed to afford 453.4 mg (52%) of the title compound as a yellow solid.

Workup

  1. temperaturecooled in an ice bath
  2. customThe cooled reaction mixture
  3. customA brown solid precipitated
  4. customis collected
  5. customchromatographed
  6. washeluting with 2% MeOH in CH2Cl2
  7. customcondensed

Sources & evidence

ORD record
ord-154b75dd263149d9a46654090047800e
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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