2-Bromo-5-fluoropyridine → benzyl {1-[5-(2,2-dimethylbutyl)-1-methyl-1H-imidazol-2-yl]-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}methylcarbamate

HRID 425392Notes

Reaction equation

HRID 425392 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([N:22]([CH3:33])[C:23](=[O:32])[O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:10]2[N:11]([CH3:21])[C:12]([CH2:15][C:16]([CH3:20])([CH3:19])[CH2:17][CH3:18])=[CH:13][N:14]=2)=[CH:4][CH:3]=1.Br[C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=1.C[Sn](C)C.C[Sn](C)C>O1CCOCC1.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:19][C:16]([CH3:20])([CH2:17][CH3:18])[CH2:15][C:12]1[N:11]([CH3:21])[C:10]([CH:9]([N:22]([CH3:33])[C:23](=[O:32])[O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=3)=[CH:3][CH:4]=2)=[N:14][CH:13]=1

Participants

7

Reactant 3

HCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 86637802benzyl {2-(4-bromophenyl)-1-[5-(2,2-dimethylbutyl)-1-methyl-1H-imidazol-2-yl]ethyl}methylcarbamate

Product 1

HCID 86637801benzyl {1-[5-(2,2-dimethylbutyl)-1-methyl-1H-imidazol-2-yl]-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}methylcarbamate

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Palladium tetrakis(triphenylphosphine) (16 mg, 0.01 mmol) was added to a degassed, ambient temperature solution of benzyl {2-(4-bromophenyl)-1-[5-(2,2-dimethylbutyl)-1-methyl-1H-imidazol-2-yl]ethyl}methylcarbamate (72 mg, 0.14 mmol), 2-bromo-5-fluoropyridine (25 mg, 0.14 mmol) and hexamethylditin (46 mg, 0.14 mmol) in 1,4-dioxane (5 mL). After stirring at reflux overnight, the reaction mixture was diluted with water and extracted with methylene chloride and ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-100% ethyl acetate/hexane afforded benzyl {1-[5-(2,2-dimethylbutyl)-1-methyl-1H-imidazol-2-yl]-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}methylcarbamate.

Workup

  1. temperatureat reflux overnight
  2. extractionextracted with methylene chloride and ethyl acetate
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6285898022bd4243b39f6140b4562368
Source dataset
uspto-grants-2012_01
Patent number
US08106070B2

Reaction notes

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