tert-Butyl acrylate → (E)-tert-Butyl 3-(3-(2-ethoxy-2-oxoethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylate

HRID 83017Notes

Reaction equation

HRID 83017 reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:42]1[CH:58]=[N:57][C:45]2[NH:46][C:47](=[O:56])[N:48]([CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:49][C:44]=2[CH:43]=1>C(#N)CC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:54]([O:53][C:51](=[O:52])[CH2:50][N:48]1[CH2:49][C:44]2[CH:43]=[C:42](/[CH:3]=[CH:2]/[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH:58]=[N:57][C:45]=2[NH:46][C:47]1=[O:56])[CH3:55]

Participants

8

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 66966289Ethyl 2-(6-bromo-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)acetate

Product 1

HCID 66967516(E)-tert-Butyl 3-(3-(2-ethoxy-2-oxoethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylateYield 60%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

tert-Butyl acrylate (1.25 mL, 8.53 mmol), diisopropylethylamine (730 μL, 4.26 mmol) and P(o-tolyl)3 (130 mg, 0.43 mmol) were successively added to a suspension of ethyl 2-(6-bromo-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)yl)acetate (670 mg, 2.13 mmol) in propionitrile (11 mL) and dimethylformamide (2.5 mL). The resulting mixture was purged with argon prior to the addition of palladium acetate (48 mg, 0.213 mmol). The mixture was purged with argon a second time and refluxed overnight. The reaction mixture was then filtered on Celite® and washed with ethyl acetate (75 mL) and dichloromethane (75 mL). The filtrate was concentrated to dryness and the residue was partitioned between dichloromethane (50 mL) and water (50 mL). The aqueous phase was separated and extracted with dichloromethane (2×100 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was precipitated from a mixture dichloromethane/diethylether to afford the title product as a white solid (460 mg, 60%).

Workup

  1. customThe resulting mixture was purged with argon
  2. customThe mixture was purged with argon a second time
  3. temperaturerefluxed overnight
  4. filtrationThe reaction mixture was then filtered on Celite®
  5. washwashed with ethyl acetate (75 mL) and dichloromethane (75 mL)
  6. concentrationThe filtrate was concentrated to dryness
  7. customthe residue was partitioned between dichloromethane (50 mL) and water (50 mL)
  8. customThe aqueous phase was separated
  9. extractionextracted with dichloromethane (2×100 mL)
  10. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL)
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe residue was precipitated from a mixture dichloromethane/diethylether

Sources & evidence

ORD record
ord-e2616a1f3bc341f2a5e99450b43a2ea2
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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