methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-furo[2,3-c]chromene-6-carboxylate → methyl 7-{4-fluoro-2-[(Z)-3-((R)-3-acetoxypyrrolidin-1-yl)-prop-1-enyl]-benzenesulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylate

HRID 1778396Notes

Reaction equation

HRID 1778396 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:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]2[C:16]([C:17]3[CH:29]=[CH:28][O:27][C:18]=3[CH2:19][O:20]2)=[CH:15][CH:14]=1)(=[O:11])=[O:10].C([Sn](CCCC)(CCCC)/[CH:35]=[CH:36]\[CH2:37][N:38]1[CH2:42][CH2:41][C@@H:40]([O:43][C:44](=[O:46])[CH3:45])[CH2:39]1)CCC>O1CCOCC1.CS(C)=O>[F:8][C:6]1[CH:5]=[CH:4][C:3]([S:9]([NH:12][C:13]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]3[C:16]([C:17]4[CH:29]=[CH:28][O:27][C:18]=4[CH2:19][O:20]3)=[CH:15][CH:14]=2)(=[O:11])=[O:10])=[C:2](/[CH:35]=[CH:36]\[CH2:37][N:38]2[CH2:42][CH2:41][C@@H:40]([O:43][C:44](=[O:46])[CH3:45])[CH2:39]2)[CH:7]=1

Participants

5

Reactant 2

HCID 66685486methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-furo[2,3-c]chromene-6-carboxylate2×HCID 66685747Acetic acid (R)-1-((Z)-3-tributylstannanylallyl)-pyrrolidin-3-yl ester2×

Product 1

HCID 68093265methyl 7-{4-fluoro-2-[(Z)-3-((R)-3-acetoxypyrrolidin-1-yl)-prop-1-enyl]-benzenesulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylateYield 86.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-furo[2,3-c]chromene-6-carboxylate (Intermediate 7, 0.09 g) and acetic acid (R)-1-((Z)-3-tributylstannylallyl)-pyrrolidin-3-yl ester (Intermediate 83, 0.170 g) in dioxane (4.5 mL) and DMSO (0.5 mL) was de-gassed and purged with argon for several minutes. tris-(Dibenzylideneacetone)dipalladium (0.017 g) and tri-tert-butylphosphonium tetrafluoroborate (0.011 g) were added and the solution was de-gassed, purged with argon and then heated at 50° C. for 2 hours. After cooling, the mixture was diluted with ethyl acetate and filtered through Celite. The filtrate was washed with water, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10% to give methyl 7-{4-fluoro-2-[(Z)-3-((R)-3-acetoxypyrrolidin-1-yl)-prop-1-enyl]-benzenesulfonylamino}-4H-furo[2,3-c]chromene-6-carboxylate (0.092 g) as a thick yellow oil which was used without further characterisation.

Workup

  1. customwas de-gassed
  2. custompurged with argon for several minutes
  3. additiontris-(Dibenzylideneacetone)dipalladium (0.017 g) and tri-tert-butylphosphonium tetrafluoroborate (0.011 g) were added
  4. customthe solution was de-gassed
  5. custompurged with argon
  6. temperatureAfter cooling
  7. additionthe mixture was diluted with ethyl acetate
  8. filtrationfiltered through Celite
  9. washThe filtrate was washed with water
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated in vacuo
  13. customthe residue was purified by chromatography on silica
  14. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%

Sources & evidence

ORD record
ord-f8e8ca95793a409da83a3e4a063ac956
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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