Tributylvinyltin → 6-Amino-2-chloro-5-vinylpyrimidine-4-carboxylic acid methyl ester

HRID 506453Notes

Reaction equation

HRID 506453 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10](I)=[C:9]([NH2:12])[N:8]=[C:7]([Cl:13])[N:6]=1)=[O:4].[CH:14]([Sn](CCCC)(CCCC)CCCC)=[CH2:15]>ClCCCl.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>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:14]=[CH2:15])=[C:9]([NH2:12])[N:8]=[C:7]([Cl:13])[N:6]=1)=[O:4]

Participants

5

Reactant 2

HCID 81998TributylvinyltinHCID 594321054-Amino-2-chloro-5-iodo-6-methoxycarbonylpyrimidine

Product 1

HCID 594320726-Amino-2-chloro-5-vinylpyrimidine-4-carboxylic acid methyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 111,2-DichloroethaneSolvent

Procedure

6-Amino-2-chloro-5-iodopyrimidine-4-carboxylic acid methyl ester (10 g, 32 mmol) was dissolved in 1,2-dichloroethane (100 mL), treated with vinyltributylstannane (11.6 mL, 12.6 g, 40 mmol) and sparged with a nitrogen stream for 10 min. Bis(triphenylphosphine)palladium(II) dichloride (1.1 g, 1.6 mmol, 5 mole %) was added and the mixture was heated at reflux under a nitrogen atmosphere for 3 h. The mixture was cooled, stirred with 10% aqueous KHF2 for 30 min, and filtered through diatomaceous earth to remove solids. The filter cake was washed with more 1,2-dichloroethane and ethyl acetate. The combined filtrates were washed with water, washed with saturated NaHCO3, washed with brine, dried, and evaporated. The crude material was chromatographed on silica (5-20% ethyl acetate/dichloromethane containing 2% acetic acid) to give the title compound (4.5 g, 70% yield). This material contained approximately 5% PPh3, but was used without further purification. MS: m/z=213. 1H NMR (CDCl3) δ 6.77 (dd, 1H), 6.4 (br, 2H), 5.70 (d, 1H), 5.61 (d, 1H).

Workup

  1. customsparged with a nitrogen stream for 10 min
  2. temperaturethe mixture was heated
  3. temperatureat reflux under a nitrogen atmosphere for 3 h
  4. temperatureThe mixture was cooled
  5. filtrationfiltered through diatomaceous earth
  6. customto remove solids
  7. washThe filter cake was washed with more 1,2-dichloroethane and ethyl acetate
  8. washThe combined filtrates were washed with water
  9. washwashed with saturated NaHCO3
  10. washwashed with brine
  11. customdried
  12. customevaporated
  13. customThe crude material was chromatographed on silica (5-20% ethyl acetate/dichloromethane containing 2% acetic acid)

Sources & evidence

ORD record
ord-1c4c084bb8194d1f82c59b8fa1cc8cf9
Source dataset
uspto-grants-2010_08
Patent number
US07786044B2

Reaction notes

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