Methylamine → 5-(5-Cyanopyridin-3-ylethynyl)-2-fluoro-N-methylbenzamide

HRID 606897Notes

Reaction equation

HRID 606897 reaction equation
CN.[C:3]([C:5]1[CH:6]=[C:7]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([F:22])=[C:17]([CH:21]=2)[C:18]([OH:20])=O)[CH:8]=[N:9][CH:10]=1)#[N:4].O.O[N:25]1[C:29]2C=CC=CC=2N=N1>O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[C:3]([C:5]1[CH:6]=[C:7]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([F:22])=[C:17]([CH:21]=2)[C:18]([NH:25][CH3:29])=[O:20])[CH:8]=[N:9][CH:10]=1)#[N:4]

Participants

7

Reactant 3

HCID 6329MethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 670476775-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid

Product 1

HCID 670476945-(5-Cyanopyridin-3-ylethynyl)-2-fluoro-N-methylbenzamideYield 68%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add N-(3-dimethylaminopropyl)-N-ethylcarbdiimide hydrochloride (120 mg, 0.62 mmol) to a mixture of methylamine (19 mg, 310 μL of a 2.0 M stock solution in tetrahydrofuran, 0.62 mmol), 5-(5-cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid), (prepared as described in EXAMPLE 120), (150 mg, 0.56 mmol) and 1-hydroxybenzotriazole hydrate (76 mg, 0.56 mmol) in N,N-dimethylformamide (2 mL), and stir for 2 h. Dilute the reaction mixture with ethyl acetate and an aqueous saturated 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 (107 mg, 68%).

Workup

  1. customan aqueous saturated solution of sodium bicarbonate and separate the layers
  2. extractionExtract the aqueous phase once with ethyl acetate
  3. washWash the combined organic phases once with an aqueous saturated solution of sodium chloride
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue by silica gel chromatography
  8. washeluting with 20:80 ethyl acetate

Sources & evidence

ORD record
ord-f0d1a8d96f1441b7868caa3d80c70f16
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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