Triethylamine → 5-(5-Chloropyridin-3-ylethynyl)-2-fluorobenzamide

HRID 606908Notes

Reaction equation

HRID 606908 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[F:10][C:11]1[CH:19]=[CH:18][C:17](I)=[CH:16][C:12]=1[C:13]([NH2:15])=[O:14].C(N(CC)CC)C>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:17]2[CH:18]=[CH:19][C:11]([F:10])=[C:12]([CH:16]=2)[C:13]([NH2:15])=[O:14])[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 235008873-Chloro-5-ethynylpyridineHCID 670478112-Fluoro-5-iodobenzamide

Product 1

HCID 670477065-(5-Chloropyridin-3-ylethynyl)-2-fluorobenzamideYield 52%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Add bis(triphenylphosphine)palladium (II) dichloride (51 mg, 0.07 mmol), copper (I) iodide (28 mg, 0.15 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.82 mmol) to a solution of 2-fluoro-5-iodobenzamide, (prepared as described in PREPARATION 44), (0.482 g, 1.82 mmol) in triethylamine (7 mL, 53 mmol) and heat at 70° C. After 10 minutes, add toluene (10 mL) to the solidified reaction mixture, heat at 70° C. for 1 h, cool to room temperature and stir overnight. Concentrate and purify the residue by silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes, to give the title compound as a white solid (260 mg, 32%).

Workup

  1. temperatureheat at 70° C. for 1 h
  2. temperaturecool to room temperature
  3. concentrationConcentrate
  4. custompurify the residue by silica gel chromatography
  5. washeluting with 50:50 to 100:0 ethyl acetate

Sources & evidence

ORD record
ord-de0e052cdf074df8a7c3b1f1c4524c8e
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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