Water → HCID 178494890, compound

HRID 2289979Notes

Reaction equation

HRID 2289979 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][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[O:22][CH3:23])=[O:9])=[CH:4][CH:3]=1.[CH2:26]([O:29][CH3:30])[C:27]#[CH:28].O>C(NCC)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:1][C:2]1[CH:25]=[CH:24][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:28]#[C:27][CH2:26][O:29][CH3:30])=[CH:15][C:14]=3[O:22][CH3:23])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 693933-MethoxypropyneHCID 178492956HCID 178492956, compound

Product 1

HCID 178494890HCID 178494890, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8021DiethylamineSolvent

Procedure

N-(4-chlorobenzyl)-4-hydroxy-6-iodo-8-methoxy-3-quinolinecarboxamide (469 mg) from Example No. 117, copper (I) iodide (57 mg), and bis(triphenylphosphine)-palladium (II) chloride (35 mg) are suspended in diethylamine (15 mL). Methyl propargyl ether (101 μL) is added and the mixture is allowed to stir at rt for 64 h. The reaction mixture is poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The organic layer is washed with saturated aqueous ammonium chloride (3×10 mL) and brine (10 mL). The aqueous layer is back-extracted with ethyl acetate (20 mL). The combined organic layers are dried (MgSO4) and concentrated. The crude product is purified by column chromatography (heptane/2-propanol, 12/1; 10/1; 5/1) to afford 188 mg (46%) of the title compound as a white solid.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe organic layer is washed with saturated aqueous ammonium chloride (3×10 mL) and brine (10 mL)
  3. extractionThe aqueous layer is back-extracted with ethyl acetate (20 mL)
  4. dry with materialThe combined organic layers are dried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product is purified by column chromatography (heptane/2-propanol, 12/1; 10/1; 5/1)

Sources & evidence

ORD record
ord-e44a183a7aec41d380cd3f73651a41cd
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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