tert-Butyl acrylate → HCID 59456913, compound

HRID 83011Notes

Reaction equation

HRID 83011 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:62]=[N:61][C:45]2[NH:46][C:47](=[O:60])[CH2:48][N:49]([CH2:51][C:52]3[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=3)[CH2:50][C:44]=2[CH:43]=1>C(#N)CC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:59][O:58][C:55]1[CH:54]=[CH:53][C:52]([CH2:51][N:49]2[CH2:50][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:62]=[N:61][C:45]=3[NH:46][C:47](=[O:60])[CH2:48]2)=[CH:57][CH:56]=1

Participants

8

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569197-Bromo-4-(4-methoxybenzyl)-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 59456913HCID 59456913, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

tert-Butyl acrylate (972 μL, 6.64 mmol), diisopropylethylamine (612 μL, 3.47 mmol) and P(o-tolyl)3 (100 mg, 0.33 mmol) were successively added to a suspension of 7-bromo-4-(4-methoxybenzyl)-4,5-dihydro-1H-pyrido[2,3-e][1,4]diazepin-2(3H)-one (600 mg, 1.66 mmol) in propionitrile (10 mL) and dimethylformamide (2 mL). The resulting mixture was then purged with argon prior to the addition of palladium acetate (40 mg, 0.16 mmol). The mixture was purged with argon a second time and refluxed overnight. The reaction mixture was then filtered on Celite®. The filtrate was concentrated to dryness and the residue was solubilized in ethyl acetate (30 mL). The aqueous phase was separated and extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (2×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/ethyl actetate (7:3) as eluent. The title product was obtained as a yellow solid (112 mg, 16%).

Workup

  1. customThe resulting mixture was then 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. concentrationThe filtrate was concentrated to dryness
  6. customThe aqueous phase was separated
  7. extractionextracted with ethyl acetate (2×40 mL)
  8. washThe combined organic phases were washed with a saturated solution of sodium chloride (2×20 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-0dd29039e3d346dd86d1d74a4dcdd565
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Reaction notes

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