HCID 71003750, compound → HCID 86712106, compound

HRID 715976Notes

Reaction equation

HRID 715976 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:22]=[CH:21][C:20]2[N:19]3[CH2:23][CH2:24][C@@H:18]3[CH2:17][O:16][C:15]=2[C:14]=1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])(=[O:11])=[O:10].[CH2:32]([N:34]([CH2:51][CH3:52])[CH2:35]/[CH:36]=[CH:37]\[Sn](CCCC)(CCCC)CCCC)[CH3:33]>O1CCOCC1.CS(C)=O>[CH2:32]([N:34]([CH2:51][CH3:52])[CH2:35]/[CH:36]=[CH:37]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:22]=[CH:21][C:20]2[N:19]3[CH2:23][CH2:24][C@@H:18]3[CH2:17][O:16][C:15]=2[C:14]=1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])(=[O:11])=[O:10])[CH3:33]

Participants

5

Reactant 2

HCID 71003750HCID 71003750, compound2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×

Product 1

HCID 86712106HCID 86712106, compoundYield 26.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of tert-butyl (R)-6-(2-bromo-4-fluorobenzenesulfonylamino)-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta[a]naphthalene-5-carboxylate (Intermediate 43, 0.061 g) and N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.096 g) in dioxane (3 mL) and DMSO (0.3 mL) was purged with nitrogen and tris-(dibenzylideneacetone)dipalladium (0) (0.006 g) and tri-tert-butylphosphonium tetrafluoroborate (0.004 g) were added. The reaction mixture was heated at 95° C., under an atmosphere of nitrogen for 1.5 hours. Further N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.096 g), tris-(dibenzylidene-acetone)dipalladium (0) (0.006 g) and tri-tert-butylphosphonium tetrafluoroborate (0.004 g) were added and heating was continued for a further 17 hours. After cooling, the mixture was diluted with ethyl acetate and washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20% to give tert-butyl (R)-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta[a]naphthalene-5-carboxylate (0.017 g) as a light brown foam.

Workup

  1. customwas purged with nitrogen and tris-(dibenzylideneacetone)dipalladium (0) (0.006 g) and tri-tert-butylphosphonium tetrafluoroborate (0.004 g)
  2. additionwere added
  3. additionFurther N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.096 g), tris-(dibenzylidene-acetone)dipalladium (0) (0.006 g) and tri-tert-butylphosphonium tetrafluoroborate (0.004 g) were added
  4. temperatureheating
  5. temperatureAfter cooling
  6. additionthe mixture was diluted with ethyl acetate
  7. washwashed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by chromatography on silica
  12. washeluting with a mixture of methanol and DCM with a gradient of 0-20%

Sources & evidence

ORD record
ord-56851383483842caa0c53911777926a4
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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