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

HRID 1508273Notes

Reaction equation

HRID 1508273 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-b9876f12c7ad45079edbefd84c0e7f8b
Source dataset
uspto-grants-2015_12
Patent number
US09221824B2

Reaction notes

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