Triethylamine → 5-(5-Chloropyridin-3-ylethynyl)-2-fluoro-N-methylbenzamide

HRID 606909Notes

Reaction equation

HRID 606909 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:20]=[CH:19][C:18](I)=[CH:17][C:12]=1[C:13]([NH:15][CH3:16])=[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:18]2[CH:19]=[CH:20][C:11]([F:10])=[C:12]([CH:17]=2)[C:13]([NH:15][CH3:16])=[O:14])[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 235008873-Chloro-5-ethynylpyridineHCID 670476742-Fluoro-5-iodo-N-methylbenzamide

Product 1

HCID 670481075-(5-Chloropyridin-3-ylethynyl)-2-fluoro-N-methylbenzamideYield 74.8%

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 (45 mg, 0.06 mmol), copper (I) iodide (26 mg, 0.14 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (200 mg, 1.45 mmol) to a solution of 2-fluoro-5-iodo-N-methylbenzamide, (prepared as described in PREPARATION 39), (0.39 g, 1.39 mmol) in triethylamine (6 mL, 43 mmol) and heat at 70° C. After 10 min, add toluene (10 mL) to the solidified reaction mixture and heat at 70° C. for 1 h. Concentrate and purify using silica gel chromatography, eluting with 40:60 ethyl acetate:hexanes, to give the title compound as a white solid (300 mg, 72%).

Workup

  1. temperatureheat at 70° C. for 1 h
  2. concentrationConcentrate
  3. custompurify
  4. washeluting with 40:60 ethyl acetate

Sources & evidence

ORD record
ord-5cbc8d4ccddb4e09842d9b8af55b7fd8
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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