4-Amino-5-bromo-2-chloropyrimidine → 2-Chloro-5-(2-ethoxyvinyl)pyrimidin-4-amine

HRID 1619125Notes

Reaction equation

HRID 1619125 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)/[CH:15]=[CH:16]\[O:17][CH2:18][CH3:19])CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:5]1[N:4]=[C:3]([NH2:9])[C:2](/[CH:15]=[CH:16]/[O:17][CH2:18][CH3:19])=[CH:7][N:6]=1

Participants

5

Reactant 2

HCID 27632934-Amino-5-bromo-2-chloropyrimidineHCID 5706773cis-1-Ethoxy-2-(tri-n-butylstannyl)ethylene2×

Product 1

HCID 112871092-Chloro-5-(2-ethoxyvinyl)pyrimidin-4-amineYield 32%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a degassed suspension of 5-bromo-2-chloropyrimidin-4-amine (preparation 37a, 2.50 g, 11.03 mmol) and (Z)-tributyl(2-ethoxyvinyl)stannane (4.76 g, 11.20 mmol) in toluene (40 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.42 g, 0.36 mmol) and the mixture was subjected to several vacuum-argon cycles and then heated to reflux for 24 hours. Further catalyst (0.42 g, 0.36 mmol) was added and the mixture was refluxed an additional 24 hours. Further (Z)-tributyl(2-ethoxyvinyl)stannane (1.20 g, 2.82 mmol) was added and the reaction was refluxed overnight. The mixture was cooled and concentrated in vacuo and the oily residue was treated with hexanes to give a solid which was purified by flash chromatography (4:1 hexanes/ethyl acetate) to give the title compound (0.70 g, 32%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 24 hours
  3. temperaturethe mixture was refluxed an additional 24 hours
  4. temperaturethe reaction was refluxed overnight
  5. temperatureThe mixture was cooled
  6. concentrationconcentrated in vacuo
  7. additionthe oily residue was treated with hexanes
  8. customto give a solid which
  9. customwas purified by flash chromatography (4:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6fe11f3a56b3461eb7c32d9f2b27ffd1
Source dataset
uspto-grants-2014_07
Patent number
US08772288B2

Reaction notes

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