Dimethylformamide → 4-[6-chloro-3-[(E)-2-(3-dimethylaminomethyl-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 82031Notes

Reaction equation

HRID 82031 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:25]([CH:26]=[CH2:27])=[N:24][N:23]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[C:18]=3[N:19]=[C:20]([Cl:22])[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[C:35]1[CH:36]=[C:37]([CH:42]=[CH:43][CH:44]=1)[CH2:38][N:39]([CH3:41])[CH3:40].C(=O)([O-])O.[Na+].CN(C)C=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:25](/[CH:26]=[CH:27]/[C:35]4[CH:44]=[CH:43][CH:42]=[C:37]([CH2:38][N:39]([CH3:41])[CH3:40])[CH:36]=4)=[N:24][N:23]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][O:29]4)[C:18]=3[N:19]=[C:20]([Cl:22])[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 6228Dimethylformamide2×HCID 516892Sodium BicarbonateHCID 17750321N-(3-Iodobenzyl)-N,N-dimethylamineHCID 86678165HCID 86678165, compound

Product 1

HCID 866781664-[6-chloro-3-[(E)-2-(3-dimethylaminomethyl-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 29%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 250 ml round bottom flask were charged 4-[6-chloro-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (1.2 g, 2.52 mmol), (3-iodo-benzyl)-dimethyl-amine (1.64 g, 6.3 mmol), tetrabutylammonium bromide (0.32 g, 1 mmol), sodium hydrogen carbonate (0.53 g, 6.3 mmol) and anhydrous dimethylformamide (42 ml). The mixture was degassed during 10 minutes using argon, palladium acetate (0.05 g, 0.25 mmol) was then added. The resulting solution was heated at 100° C. under argon overnight. Dimethylformamide was eliminated under vacuum, dichloromethane and water were added to the residue, after extraction the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product. Further purification on a silica gel column chromatography using a gradient of methanol (0-5%) in dichloromethane afforded the title compound as brown solid (0.44 g, 29%).

Workup

  1. customThe mixture was degassed during 10 minutes
  2. additionwas then added
  3. additionwere added to the residue
  4. extractionafter extraction the organic layer
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product
  9. customFurther purification on a silica gel column chromatography

Sources & evidence

ORD record
ord-3606554562b54fb39969ef5d5395b586
Source dataset
uspto-grants-2014_09
Patent number
US08846712B2

Reaction notes

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