Triethylamine → (E)-Ethyl 3-(4-(isopropylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl)acrylate

HRID 886795Notes

Reaction equation

HRID 886795 reaction equation
I[C:2]1[C:3]([NH:11][CH:12]([CH3:14])[CH3:13])=[N:4][C:5]([S:9][CH3:10])=[N:6][C:7]=1[CH3:8].[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[CH:16]=[CH2:17].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(N(C)C)=O>[CH:12]([NH:11][C:3]1[C:2](/[CH:17]=[CH:16]/[C:15]([O:19][CH2:20][CH3:21])=[O:18])=[C:7]([CH3:8])[N:6]=[C:5]([S:9][CH3:10])[N:4]=1)([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 576069565-Iodo-N-isopropyl-6-methyl-2-(methylthio)pyrimidin-4-amine

Product 1

HCID 57606959(E)-Ethyl 3-(4-(isopropylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl)acrylateYield 34%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Iodo-N-isopropyl-6-methyl-2-(methylthio)pyrimidin-4-amine (8.1 g, 26.2 mmol), ethyl acrylate (5.24 g, 52.4 mmol), triethylamine (10.6 g, 105 mmol), palladium (II) acetate (1.17 g, 5.23 mmol), and tri-o-tolyl phosphine (1.59 g, 5.23 mmol) were added in that order to 10.8 mL of DMA in a pressure tube and sealed. The reaction mixture was heated to 100° C. and allowed to stir overnight. The reaction was quenched by filtration through a short silica plug washing with ACN. The solvent was evaporated and diluted with ethyl acetate then extracted with 10% aqueous LiCl, followed by water and brine. NOTE: Extraction is necessary to remove all DMA giving resolution in chromatography. The sample was purified by silica gel column chromatography using 20% ethyl acetate/hexane as eluent. Desired fractions were combined and reduced to afford 2.5 g (34% yield) of ethyl (2E)-3-[4-(isopropylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl]acrylate as a yellow/orange oil.

Workup

  1. customsealed
  2. customThe reaction was quenched by filtration through a short silica plug
  3. washwashing with ACN
  4. customThe solvent was evaporated
  5. additiondiluted with ethyl acetate
  6. extractionthen extracted with 10% aqueous LiCl
  7. extractionExtraction
  8. customto remove all DMA giving resolution in chromatography
  9. customThe sample was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-51df751b5de649b180e22e3969d66feb
Source dataset
uspto-grants-2012_08
Patent number
US08247408B2

Reaction notes

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