4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → HCID 86676021, compound

HRID 2172395Notes

Reaction equation

HRID 2172395 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.C([Sn](CCCC)(CCCC)[C:20]([O:22][CH2:23][CH3:24])=[CH2:21])CCC.[F-].[K+]>CN(C)C=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>[CH2:23]([O:22][C:20]([C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1)=[CH2:21])[CH3:24]

Participants

6

Reactant 3

HCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-

Product 1

HCID 86676021HCID 86676021, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (10 g, 43.0 mmol), tributyl(1-ethoxyvinyl)stannane (16 ml, 47.3 mmol) and bis(triphenylphosphine)palladium dichloride (1.508 g, 2.149 mmol) in N,N-dimethylformamide (100 mL) was heated to 70° C. for 5 hours. After cooling, the mixture was treated with an aqueous solution of KF (6 g in 12 mL water) and stirred over the weekend at room temperature. The mixture was filtered through diatomaceous earth and washed with ethyl acetate. The filtrate was partitioned between ethyl acetate and brine. The organic phase was washed with brine twice and concentrated. The residue was separated by flash chromatography (0-20% gradient ethyl acetate in hexane) to give the title compound. MS (DCI/NH3) m/z 269 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. filtrationThe mixture was filtered through diatomaceous earth
  3. washwashed with ethyl acetate
  4. customThe filtrate was partitioned between ethyl acetate and brine
  5. washThe organic phase was washed with brine twice
  6. concentrationconcentrated
  7. customThe residue was separated by flash chromatography (0-20% gradient ethyl acetate in hexane)

Sources & evidence

ORD record
ord-3b50c60d9ea04466a6ba3f55661ad320
Source dataset
uspto-grants-2015_06
Patent number
US09051327B2

Reaction notes

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