2-Bromo-5-fluoropyridine → 2-(4-(5-Fluoropyridin-2-yl)but-3-ynyl)-imidazo[1,2-a]pyridine

HRID 334573Notes

Reaction equation

HRID 334573 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[CH2:9]([C:13]1[N:14]=[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]2[CH:21]=1)[CH2:10][C:11]#[CH:12]>C(N(CC)CC)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:12]#[C:11][CH2:10][CH2:9][C:13]2[N:14]=[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]3[CH:21]=2)=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 27831712-Bromo-5-fluoropyridineHCID 707005722-(But-3-YN-1-YL)imidazo[1,2-A]pyridine

Product 1

HCID 665977412-(4-(5-Fluoropyridin-2-yl)but-3-ynyl)-imidazo[1,2-a]pyridineYield 8.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent2×

Procedure

In a dry reaction tube containing in suspension copper iodide (6.5 mg, 0.03 mmol) and triethylamine (2.3 mL), were added 2-bromo-5-fluoropyridine (120 mg, 0.68 mmol) and Pd(PPh3)2Cl2 (39 mg, 0.03 mmol) under N2. A yellow suspension was obtained after 5 min of stirring at room temperature. A solution of 2-(but-3-ynyl)-imidazo[1,2-a]pyridine (120 mg, 0.68 mmol) in triethylamine (0.5 mL) was then added under N2. Immediately the color of the reaction turns to black. The mixture was stirred at room temperature for 30 min and heated at 80° C. overnight. The reaction mixture was concentrated and the crude product was purified by Flash chromatography (prepacked 25 g silicagel column, DCM/MeOH from 100/0 to 97/3 as eluent) to afford 15 mg of 2-(4-(5-fluoropyridin-2-yl)but-3-ynyl)-imidazo[1,2-a]pyridine (Yield: 8%) as a brown semi-solid.

Workup

  1. customIn a dry reaction tube
  2. customA yellow suspension was obtained after 5 min
  3. stirringThe mixture was stirred at room temperature for 30 min
  4. temperatureheated at 80° C. overnight
  5. concentrationThe reaction mixture was concentrated
  6. customthe crude product was purified by Flash chromatography (prepacked 25 g silicagel column, DCM/MeOH from 100/0 to 97/3 as eluent)

Sources & evidence

ORD record
ord-6f38cd2ea53348a99d5eaad8eb08762c
Source dataset
uspto-grants-2014_11
Patent number
US08883826B2

Reaction notes

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