Diisopropylethylamine → 4-(2-Chloro-6-iodopyridin-3-yloxy)-6,7-dimethoxyquinoline

HRID 1010223Notes

Reaction equation

HRID 1010223 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:22]([OH:23])=[CH:21][CH:20]=[C:19]([I:24])[N:18]=1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C.O1CCCC1>CN(C)C=O.CCCCCC.C(OCC)(=O)C.O>[Cl:16][C:17]1[C:22]([O:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[CH:21][CH:20]=[C:19]([I:24])[N:18]=1

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 4596104-Chloro-6,7-dimethoxyquinolineHCID 107774172-Chloro-3-hydroxy-6-iodopyridineHCID 21939870Tetrahydrofuran ethyl acetate

Product 1

HCID 229365854-(2-Chloro-6-iodopyridin-3-yloxy)-6,7-dimethoxyquinolineYield 49%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-6,7-dimethoxyquinoline (2.23 g, 10.0 mmol), 2-chloro-6-iodopyridin-3-ol (2.55 g, 22.0 mmol) and diisopropylethylamine (1.29 g, 10.0 mmol) were heated and stirred in dimethylformamide (5 ml) at 130° C. for 3 hours. The reaction solution was distributed between an ethyl acetate-tetrahydrofuran mixed solvent and water, the organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent—ethyl acetate:hexane=3:1), and the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, after which the crystals were filtered out, washed with hexane and then blow-dried to obtain the title compound (2.16 g, 4.88 mmol, 49%) as colorless crystals.

Workup

  1. washthe organic layer was washed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationthe drying agent was filtered off
  4. distillationthe filtrate was distilled off under reduced pressure
  5. customThe obtained crude product
  6. additionthe fraction containing the target substance
  7. concentrationwas concentrated
  8. additiondiluted with hexane
  9. filtrationafter which the crystals were filtered out
  10. washwashed with hexane
  11. customblow-dried

Sources & evidence

ORD record
ord-840bffd5299d4a248a86ea66875ed3f1
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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