Ethyl 1-propenyl ether → 2-Chloro-5-(2-ethoxy-vinyl)-pyrimidin-4-ylamine

HRID 1966391Notes

Reaction equation

HRID 1966391 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH2:10]([O:12][CH:13]=[CH:14]C)[CH3:11].COCCOC.C1(C)C=CC=CC=1.O.CCO>[N+](CC)(CC)(CC)CC.[Cl-].O.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:8][C:5]1[N:4]=[C:3]([NH2:9])[C:2]([CH:11]=[CH:10][O:12][CH2:13][CH3:14])=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 13570Ethyl 1-propenyl etherHCID 27632934-Amino-5-bromo-2-chloropyrimidineHCID 21931398DME H2O Toluene EtOH

Product 1

HCID 573489732-Chloro-5-(2-ethoxy-vinyl)-pyrimidin-4-ylamine

Reagents, catalysts & solvents 3

HCID 5946Tetraethylammonium ChlorideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

5-Bromo-2-chloro-pyrimidin-4-ylamine (88.0 g, 0.43 mol), 1-ethoxy-propene (220 g, 0.49 mol), Pd(PPh3)2Cl2 (35.0 g, 0.05 mol) and Et4NCl (67.0 g, 0.40 mol) are suspended in solvent (750 mL, DME/toluene/H2O/EtOH 10:1:3:6) under nitrogen. The reaction mixture is heated to reflux for 24 h, cooled to rt, and then diluted with water. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are dried over MgSO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography (SiO2, gradient elution, EtOAc/petroleumether 1:10>1:4) to yield the title compound as a yellow solid.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux for 24 h
  3. extractionThe aqueous layer is extracted with EtOAc (3×)
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography (SiO2, gradient elution, EtOAc/petroleumether 1:10>1:4)

Sources & evidence

ORD record
ord-622f2cff3afb4e788f4ff809fab9a08f
Source dataset
uspto-grants-2013_04
Patent number
US08420657B2

Reaction notes

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