methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate → methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate

HRID 595110Notes

Reaction equation

HRID 595110 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[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:17]2[O:18][CH2:19][C:20]3[N:21]([CH:22]=[CH:23][CH:24]=3)[C:16]2=[CH:15][CH:14]=1)(=[O:11])=[O:10].[CH2:30]([N:32]([CH2:49][CH3:50])[CH2:33]/[CH:34]=[CH:35]\[Sn](CCCC)(CCCC)CCCC)[CH3:31]>O1CCOCC1.CS(C)=O>[CH2:30]([N:32]([CH2:49][CH3:50])[CH2:33]/[CH:34]=[CH:35]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:17]2[O:18][CH2:19][C:20]3[N:21]([CH:22]=[CH:23][CH:24]=3)[C:16]2=[CH:15][CH:14]=1)(=[O:11])=[O:10])[CH3:31]

Participants

5

Reactant 2

HCID 70983589methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×

Product 1

HCID 86712813methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylateYield 64.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 16, 0.107 g) and N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.179 g) in dioxane (3 mL) and DMSO (0.3 mL) was degassed and purged with nitrogen. Tris-(dibenzylideneacetone)dipalladium (0) (0.01 g) and tri-tert-butylphosphonium tetrafluoroborate (0.006 g) were added and the mixture was degassed and purged with nitrogen again, then the mixture was heated to 95° C. for 1 hour. After cooling, the mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with more ethyl acetate and the combined organic layers were dried (MgSO4) 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 0-5% to give methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-4H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (0.074 g) as a sticky yellow oil.

Workup

  1. customwas degassed
  2. custompurged with nitrogen
  3. additionTris-(dibenzylideneacetone)dipalladium (0) (0.01 g) and tri-tert-butylphosphonium tetrafluoroborate (0.006 g) were added
  4. customthe mixture was degassed
  5. custompurged with nitrogen again
  6. temperatureAfter cooling
  7. customthe mixture was partitioned between ethyl acetate and water
  8. extractionThe aqueous layer was extracted with more ethyl acetate
  9. dry with materialthe combined organic layers were dried (MgSO4)
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe residue was purified by chromatography on silica
  13. washeluting with a mixture of methanol and DCM with a gradient of 0-5%

Sources & evidence

ORD record
ord-5d279f218f06492c8ac45c9c0064c942
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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