N,N,N',N'-Tetramethylethylenediamine → 2-Fluoro-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzonitrile

HRID 452031Notes

Reaction equation

HRID 452031 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:43][N:44](C)CCN(C)C.Br[C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:59]=[N:60][C:61]3[N:62]([C:64]([CH2:67][C:68]4[CH:69]=[C:70]5[C:75](=[CH:76][CH:77]=4)[N:74]=[CH:73][CH:72]=[CH:71]5)=[CH:65][N:66]=3)[N:63]=2)=[CH:54][C:53]=1[F:78]>CN(C)C=O.[C-]#N.[Zn+2].[C-]#N.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]>[F:78][C:53]1[CH:54]=[C:55]([C:58]2[CH:59]=[N:60][C:61]3[N:62]([C:64]([CH2:67][C:68]4[CH:69]=[C:70]5[C:75](=[CH:76][CH:77]=4)[N:74]=[CH:73][CH:72]=[CH:71]5)=[CH:65][N:66]=3)[N:63]=2)[CH:56]=[CH:57][C:52]=1[C:43]#[N:44]

Participants

7

Reactant 3

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 579711886-((2-(4-Bromo-3-fluorophenyl)imidazo[1,2-b][1,2,4]triazin-7-yl)methyl)quinoline

Product 1

HCID 445128962-Fluoro-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

Zinc cyanide (131 mg, 1.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol) (Aldrich, Cat. #328774), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis-(diphenylphosphine) (78.5 mg, 0.136 mmol) (Aldrich, Cat. #526460), and N,N,N′,N′-tetramethylethylenediamine (0.22 mL, 1.4 mmol) were added successively to a mixture of 6-[2-(4-bromo-3-fluorophenyl)imidazo[1,2-b][1,2,4]-triazin-7-yl]methylquinoline (Step 8, 480 mg, 1.10 mmol) in N,N-dimethylformamide (8.7 mL) in a microwave tube. The tube was sealed and degassed three times and heated to 160° C. under microwave irradiation for 500 s. Most of the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, water and brine, and dried over magnesium sulfate. Filtration and concentration afforded a residue which was purified on a silica gel column with methanol in dichloromethane (0-6%) to give the desired product. (90%) LCMS (M+H)+: m/z=381.0.

Workup

  1. customThe tube was sealed
  2. customdegassed three times
  3. customMost of the solvent was removed under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed with aqueous sodium bicarbonate, water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration and concentration
  8. customafforded a residue which
  9. customwas purified on a silica gel column with methanol in dichloromethane (0-6%)

Sources & evidence

ORD record
ord-9e5774c764d847d6a6d46ce2d5645560
Source dataset
uspto-grants-2013_07
Patent number
US08487096B2

Reaction notes

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