Stannane, tributyl(1-ethoxyethenyl)- → (S)-2-(1-((9-(1-ethoxyvinyl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

HRID 1398389Notes

Reaction equation

HRID 1398389 reaction equation
Br[C:2]1[C:18]([O:19][CH2:20][C@@H:21]([N:26]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]2=[O:36])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14].C([Sn](CCCC)(CCCC)[C:42]([O:44][CH2:45][CH3:46])=[CH2:43])CCC>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:45]([O:44][C:42]([C:2]1[C:18]([O:19][CH2:20][C@@H:21]([N:26]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]2=[O:36])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14])=[CH2:43])[CH3:46]

Participants

6

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86710375(S)-2-(1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

Product 1

HCID 86710376(S)-2-(1-((9-(1-ethoxyvinyl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dioneYield 72%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (S)-2-(1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (100 mg, 0.182 mmol), tributyl(1-ethoxyvinyl)stannane (132 mg, 0.365 mmol), DPPF (20.22 mg, 0.036 mmol) and Pd2(dba)3 (16.70 mg, 0.018 mmol) in 1,4-dioxane (5 mL) was purged with nitrogen for 5 min then heated at 100° C. overnight. After cooling to ambient temperature, the volatiles were concentrated under reduced pressure. The residue was taken up in ethyl acetate and filtered through diatomaceous earth (Celite®). The organic filtrate was washed with H2O, then brine, dried over Na2SO4 and concentrated under reduced pressure to afford (S)-2-(1-((9-(1-ethoxyvinyl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (0.15 g, 0.131 mmol, 72% crude yield) as a black gummy solid. The material was carried forward without further purification. LC/MS (ESI) m/e 540.3 [(M+H)+, calcd for C32H34N3O5 540.2; LC/MS retention time (method G): tR=1.21 min.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe volatiles were concentrated under reduced pressure
  3. filtrationfiltered through diatomaceous earth (Celite®)
  4. washThe organic filtrate was washed with H2O
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6a1db6a652a643c5a3219c4734c96d1e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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