Acrylamide → (2E)-3-[3-(4,4-dibutyl-7-fluoro-1-hydroxy-3-oxo-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]acrylamide

HRID 494492Notes

Reaction equation

HRID 494492 reaction equation
[CH2:1]([C:5]1([CH2:31][CH2:32][CH2:33][CH3:34])[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[C:8]([OH:16])=[C:7]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25](I)=[CH:26][C:20]=3[S:19](=[O:29])(=[O:28])[N:18]=2)[C:6]1=[O:30])[CH2:2][CH2:3][CH3:4].[C:35]([NH2:39])(=[O:38])[CH:36]=[CH2:37].C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([C:5]1([CH2:31][CH2:32][CH2:33][CH3:34])[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[C:8]([OH:16])=[C:7]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25](/[CH:37]=[CH:36]/[C:35]([NH2:39])=[O:38])=[CH:26][C:20]=3[S:19](=[O:29])(=[O:28])[N:18]=2)[C:6]1=[O:30])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 6579AcrylamideHCID 8471TriethylamineHCID 1364037811,1-Dibutyl-6-fluoro-4-hydroxy-3-(7-iodo-1,1-dioxido-4h-1,2,4-benzothiadiazin-3-yl)naphthalen-2(1h)-one

Product 1

HCID 136375604(2E)-3-[3-(4,4-dibutyl-7-fluoro-1-hydroxy-3-oxo-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]acrylamideYield 56%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of the compound of Example 20B (65 mg, 0.11 mmol), acrylamide (9 mg, 0.12 mmol), triethylamine (45 μL, 0.33 mmol), and palladium (II) acetate (1.2 mg, 0.005 mmol) in N,N-dimethylformamide (1.5 mL) in a resealable pressure tube was degassed by evacuation and purging with nitrogen. The pressure tube was sealed and warmed at 100° C. for 1 h. The solution was cooled and diluted with ethyl acetate and water. The mixture was acidified by addition of citric acid solution (1 M, 2 mL). The organic layer was extracted with water (2×) and with saturated NaCl solution. Drying (Na2SO4) and concentration in vacuo afforded a solid, which was purified by flash chromatography eluting with methanol in dichloromethane. These procedures afforded the title compound (33 mg, 56%) as a light amber solid.

Workup

  1. custompurging with nitrogen
  2. customThe pressure tube was sealed
  3. temperatureThe solution was cooled
  4. additiondiluted with ethyl acetate and water
  5. additionThe mixture was acidified by addition of citric acid solution (1 M, 2 mL)
  6. extractionThe organic layer was extracted with water (2×) and with saturated NaCl solution
  7. customDrying
  8. concentration(Na2SO4) and concentration in vacuo
  9. customafforded a solid, which
  10. customwas purified by flash chromatography
  11. washeluting with methanol in dichloromethane

Sources & evidence

ORD record
ord-8d1cff42620b4d1caadebb9956146272
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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