methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-furo[2,3-c]chromene-6-carboxylate → methyl 7-[2-((Z)-3-{pyrrolidin-1-yl}prop-1-enyl)-4-fluorobenzene-sulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylate

HRID 1778376Notes

Reaction equation

HRID 1778376 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][CH2:40][CH2:39]1)CCC>CS(C)=O.O1CCOCC1>[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][CH2:40][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 666864121-((Z)-3-tributylstannanylallyl)pyrrolidine2×

Product 1

HCID 66693484methyl 7-[2-((Z)-3-{pyrrolidin-1-yl}prop-1-enyl)-4-fluorobenzene-sulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylateYield 38.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino)-4H-furo[2,3-c]chromene-6-carboxylate (Intermediate 7, 0.300 g) and 1-((Z)-3-tributylstannanyl-allyl)-pyrrolidine (Intermediate 54, 0.390 g) in DMSO (2 mL) and dioxane (8 mL) was de-gassed and purged with nitrogen before tris-(dibenzylideneacetone)dipalladium (0) (0.076 g) and tri-tert-butylphosphonium tetrafluoroborate (0.048 g) were added and the mixture was heated at 90° C. for 3 hours. After cooling, the mixture was diluted with ethyl acetate and filtered. 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%. The resultant product was triturated with ether to give methyl 7-{4-fluoro-2-[(Z)-3-(pyrrolidin-1-yl)prop-1-enyl]benzenesulfonyl-amino}-4H-furo[2,3-c]chromene-6-carboxylate (0.124 g), as a pale orange solid.

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen before tris-(dibenzylideneacetone)dipalladium (0) (0.076 g) and tri-tert-butylphosphonium tetrafluoroborate (0.048 g)
  3. additionwere added
  4. temperatureAfter cooling
  5. additionthe mixture was diluted with ethyl acetate
  6. filtrationfiltered
  7. washThe filtrate was washed with water
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by chromatography on silica
  12. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%
  13. customThe resultant product was triturated with ether

Sources & evidence

ORD record
ord-0df1a09e55084edb845d540ac3427f93
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

Loading…