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

HRID 83031Notes

Reaction equation

HRID 83031 reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].[CH:10]([N:13]([CH:16]([CH3:18])C)[CH2:14][CH3:15])([CH3:12])C.[CH3:19]C1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:42]1[CH:43]=[C:44]2[NH:50][C:49](=[O:51])[NH:48][C:45]2=[N:46][CH:47]=1.[C:52](#[N:55])CC>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:52][N:55]1[CH2:15][CH2:14][N:13]([CH2:10][CH2:12][N:50]2[CH2:19][C:44]3[CH:43]=[C:42](/[CH:3]=[CH:2]/[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH:47]=[N:46][C:45]=3[NH:48][C:49]2=[O:51])[CH2:16][CH2:18]1

Participants

8

Reactant 5

HCID 7854PropionitrileHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 19244136-bromo-3H-imidazo[4,5-b]pyridin-2-ol

Product 1

HCID 68338119(E)-tert-Butyl 3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylateYield 56%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

tert-Butyl acrylate (2.74 mL, 18.6 mmol), diisopropylethylamine (1.6 mL, 9.8 mmol) and P(o-tolyl)3 (272 mg, 0.89 mmol) were successively added to a suspension of 6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one (1.0 g, 4.67 mmol) in propionitrile (27 mL) and dimethylformamide (7 mL) at room temperature. The resulting mixture was purged with argon prior to the addition of palladium acetate (100 mg, 0.44 mmol). The mixture was then purged with argon a second time and refluxed overnight. The reaction mixture was filtered on Celite® and the filtrate was concentrated to dryness. The residue was partitioned between ethyl acetate (20 mL) and water (30 mL). The organic phase was washed with a saturated solution of sodium chloride (2×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was triturated in diethyl ether to give the title product as a brown solid (667 mg, 56%).

Workup

  1. customThe resulting mixture was purged with argon
  2. customThe mixture was then purged with argon a second time
  3. temperaturerefluxed overnight
  4. filtrationThe reaction mixture was filtered on Celite®
  5. concentrationthe filtrate was concentrated to dryness
  6. customThe residue was partitioned between ethyl acetate (20 mL) and water (30 mL)
  7. washThe organic phase was washed with a saturated solution of sodium chloride (2×30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-90639de35b084243b9cda134fefce179
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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