Tri-tert-butylphosphine tetrafluoroborate → methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-10H-9-oxa-1,2-diazaphenanthrene-8-carboxylate

HRID 2200332Notes

Reaction equation

HRID 2200332 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:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]2[C:16]([C:17]3[CH:18]=[CH:19][N:20]=[N:21][C:22]=3[CH2:23][O:24]2)=[CH:15][CH:14]=1)(=[O:11])=[O:10].[CH2:31]([N:33]([CH2:50][CH3:51])[CH2:34]/[CH:35]=[CH:36]\[Sn](CCCC)(CCCC)CCCC)[CH3:32].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.CS(C)=O.C(OCC)(=O)C.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]>[CH2:31]([N:33]([CH2:50][CH3:51])[CH2:34]/[CH:35]=[CH:36]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]2[C:16]([C:17]3[CH:18]=[CH:19][N:20]=[N:21][C:22]=3[CH2:23][O:24]2)=[CH:15][CH:14]=1)(=[O:11])=[O:10])[CH3:32]

Participants

8

Reactant 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborate2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine4×HCID 89705396methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-10H-9-oxa-1,2-diazaphenanthrene-8-carboxylate2×

Product 1

HCID 89705427methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-10H-9-oxa-1,2-diazaphenanthrene-8-carboxylateYield 58.9%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-10H-9-oxa-1,2-diazaphenanthrene-8-carboxylate (Intermediate 5, 0.403 g), N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 2, 0.656 g), tris(dibenzylidene-acetone)dipalladium(0) (0.037 g) and tri-tert-butylphosphonium tetrafluoroborate (0.024 g) in dioxan (10 mL) and DMSO (1 mL) was stirred and heated at 95° C. under nitrogen for 90 minutes. Further N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 2, 0.656 g), tris(dibenzylideneacetone)dipalladium(0) (0.037 g) and tri-tert-butylphosphonium tetrafluoroborate (0.024 g) were added and the mixture was heated at 95° C. under nitrogen for a further 45 minutes. After cooling, the mixture was diluted with ethyl acetate and washed three times with water. The combined aqueous extracts were extracted with DCM and the combined organic layers were filtered through a phase separator. The filtrate was evaporated 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 methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-10H-9-oxa-1,2-diazaphenanthrene-8-carboxylate (0.253 g) as a sandy coloured solid.

Workup

  1. temperaturethe mixture was heated at 95° C. under nitrogen for a further 45 minutes
  2. temperatureAfter cooling
  3. washwashed three times with water
  4. extractionThe combined aqueous extracts were extracted with DCM
  5. filtrationthe combined organic layers were filtered through a phase separator
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-20%

Sources & evidence

ORD record
ord-615f058410a745a2adb3a45b25e601c3
Source dataset
uspto-grants-2016_06
Patent number
US09359369B2

Reaction notes

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