Triethylamine → tert-butyl 2-{1-{[(benzyloxy)carbonyl]amino}-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate

HRID 1881466Notes

Reaction equation

HRID 1881466 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:21]1[N:22]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:23]=[C:24]([CH2:26][C:27]([CH3:31])([CH3:30])[CH2:28][CH3:29])[N:25]=1)[CH2:13][C:14]1[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][N:41]=1.C[Sn](C)C.C[Sn](C)C.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>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]>[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:21]1[N:22]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:23]=[C:24]([CH2:26][C:27]([CH3:31])([CH3:30])[CH2:28][CH3:29])[N:25]=1)[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[CH:42][N:41]=2)=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 66705603tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate

Product 1

HCID 66705640tert-butyl 2-{1-{[(benzyloxy)carbonyl]amino}-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate

Reagents, catalysts & solvents 3

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

Procedure

Palladium tetrakis(triphenylphosphine) (69 mg, 0.06 mmol) was added to a degassed, ambient temperature solution of tert-butyl 2-[1-{[(benzyloxy)carbonyl]amino}-2-(4-bromophenyl)ethyl]-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate (for synthesis see Example 37) (324 mg, 0.60 mmol), 2-bromo-5-fluoropyridine (105 mg, 0.60 mmol) and hexamethylditin (195 mg, 0.60 mmol) in 1,4-dioxane (15 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. Triethylamine (0.25 mL, 1.79 mmol) followed by di-tert-butyl dicarbonate (260 mg, 1.19 mmol) were added to an ambient temperature solution of the crude residue and N,N-dimethylaminopyridine (catalytic). After stirring at ambient temperature for 1 h, the reaction mixture was quenched with water and extracted with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-50% ethyl acetate/hexane afforded tert-butyl 2-{1-{[(benzyloxy)carbonyl]amino}-2-[4-(5-fluoropyridin-2-yl)phenyl]ethyl}-4-(2,2-dimethylbutyl)-1H-imidazole-1-carboxylate.

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
  5. stirringAfter stirring at ambient temperature for 1 h
  6. customthe reaction mixture was quenched with water
  7. extractionextracted with methylene chloride
  8. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4b7c02d75fc0444d867535c8fdd90689
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

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