Ammonia → 5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzamide

HRID 606896Notes

Reaction equation

HRID 606896 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[CH:12]=[CH:13][C:14]([F:20])=[C:15]([CH:19]=2)[C:16](O)=[O:17])[CH:6]=[N:7][CH:8]=1)#[N:2].O.O[N:23]1C2C=CC=CC=2N=N1.N>CN(C)C=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[CH:12]=[CH:13][C:14]([F:20])=[C:15]([CH:19]=2)[C:16]([NH2:23])=[O:17])[CH:6]=[N:7][CH:8]=1)#[N:2]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 27960291-Hydroxybenzotriazole hydrateHCID 670476775-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid

Product 1

HCID 670479155-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzamideYield 42.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add N-(3-dimethylaminopropyl)-N-ethylcarbodiamide hydrochloride (128 mg, 0.66 mmol) to a solution of 5-(5-cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid (prepared as described in EXAMPLE 120), (158 mg, 0.59 mmol) and 1-hydroxybenzotriazole hydrate (87 mg, 0.64 mmol) in N,N-dimethylformamide (5 mL) and stir for 5 min to form a gel. Add additional N,N-dimethylformamide (4 mL) to enable stirring of the reaction mixture and stir for 0.5 h. Bubble anhydrous ammonia gas through the reaction mixture for 1-2 min. and then stir for an additional 15 min. Dilute the reaction mixture with ethyl acetate and a saturated aqueous solution of sodium bicarbonate and separate the layers. Extract the aqueous phase once with ethyl acetate. Wash the combined organic phases once with an aqueous saturated solution of sodium chloride, dry (sodium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting with 20:80 ethyl acetate:dichloromethane, to give the title compound as a white solid (66 mg, 42%).

Workup

  1. customto form a gel
  2. stirringto enable stirring of the reaction mixture
  3. stirringstir for 0.5 h
  4. stirringstir for an additional 15 min
  5. customa saturated aqueous solution of sodium bicarbonate and separate the layers
  6. extractionExtract the aqueous phase once with ethyl acetate
  7. washWash the combined organic phases once with an aqueous saturated solution of sodium chloride
  8. dry with materialdry (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify the residue by silica gel chromatography
  12. washeluting with 20:80 ethyl acetate

Sources & evidence

ORD record
ord-28cc79edb88b44bbbf991f58cd2b1190
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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