Triethylamine → 4-[2-Cyclopropyl-1-(4-fluoro-phenyl)-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

HRID 860155Notes

Reaction equation

HRID 860155 reaction equation
[CH:1]1([C:4]2[N:5]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:6]=[C:7](I)[N:8]=2)[CH2:3][CH2:2]1.[CH3:17][C:18]1[CH:23]=[C:22]([C:24]#[C:25][Si](C)(C)C)[CH:21]=[CH:20][N:19]=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]1([C:4]2[N:5]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:6]=[C:7]([C:25]#[C:24][C:22]3[CH:21]=[CH:20][N:19]=[C:18]([CH3:17])[CH:23]=3)[N:8]=2)[CH2:3][CH2:2]1

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 219853962-Methyl-4-((trimethylsilyl)ethynyl)pyridineHCID 691201812-Cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole

Product 1

HCID 100415194-[2-Cyclopropyl-1-(4-fluoro-phenyl)-1H-imidazol-4-ylethynyl]-2-methyl-pyridineYield 59%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

2-Cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole (V-1) (150 mg, 0.46 mmol) and 2-methyl-4-trimethylsilanylethynyl-pyridine (113 mg, 0.59 mmol) were dissolved in 4 mL dry THF. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. In a second reaction vessel triphenylphosphine (4 mg, 0.01 mmol), bis(triphenylphosphine)-palladium(II)chloride (16 mg, 0.02 mmol), copper(I)iodide (1 mg, 0.01 mmol) and triethyl amine (0.10 mL, 0.69 mmol) were dissolved in 2 mL dry THF. This mixture was also evacuated and backfilled with argon several times to remove oxygen from the solution. This mixture was heated to 40° C. and the solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise. The reaction mixture was heated to 60° C. and tetrabutylammonium fluoride solution (1M in THF, 0.72 mL, 0.69 mmol) was added dropwise during 5 min. The reaction was than stirred at 40° C. for 2 hours. The mixture was taken up in 20 mL water and extracted three times with ethyl acetate (20 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4) to obtain the desired title compound as a colorless solid (85 mg, 59%),

Workup

  1. customThis mixture was evacuated
  2. customto remove oxygen from the solution
  3. customThis mixture was also evacuated
  4. customto remove oxygen from the solution
  5. additionthe solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise
  6. temperatureThe reaction mixture was heated to 60° C.
  7. extractionextracted three times with ethyl acetate (20 mL each)
  8. dry with materialThe combined organic extracts were dried with magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4)

Sources & evidence

ORD record
ord-79504f27139041e1a1d29206bcbe4bcb
Source dataset
uspto-grants-2006_12
Patent number
US07153874B2

Reaction notes

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