Tri-tert-butylphosphine tetrafluoroborate → methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate

HRID 595115Notes

Reaction equation

HRID 595115 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[C:19]3=[CH:23][CH:24]=[N:25][N:18]3[CH2:17][CH2:16][C:15]=2[C:14]=1[C:26]([O:28][CH3:29])=[O:27])(=[O:11])=[O:10].[CH2:30]([N:32]([CH2:49][CH3:50])[CH2:33]/[CH:34]=[CH:35]\[Sn](CCCC)(CCCC)CCCC)[CH3:31].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.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]>[CH2:30]([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[CH:22]=[CH:21][C:20]2[C:19]3=[CH:23][CH:24]=[N:25][N:18]3[CH2:17][CH2:16][C:15]=2[C:14]=1[C:26]([O:28][CH3:29])=[O:27])(=[O:11])=[O:10])[CH3:31]

Participants

6

Reactant 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 70984117Methyl 8-(2-bromo-4-fluorobenzenesulfonylamino)-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×

Product 1

HCID 86712814methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylateYield 60.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 8-(2-bromo-4-fluorobenzenesulfonylamino)-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 21, 0.088 g), N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.222 g), tris-(dibenzylideneacetone)dipalladium (0) (0.020 g) and tri-tert-butylphosphonium tetrafluoroborate (0.01 g) in dioxane (3 mL) was de-gassed and purged with nitrogen and then heated to 80° C. in a sealed vessel for 2 hours. The resultant mixture was cooled, filtered through Celite and washed with ethyl acetate. 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 0-10% to give methyl 8-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.057 g) as a glass.

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. temperatureThe resultant mixture was cooled
  4. filtrationfiltered through Celite
  5. washwashed with ethyl acetate
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-10%

Sources & evidence

ORD record
ord-712940338e55471f82a9ba668eefa4d1
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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