Dimethylamine, hydrochloride → 5-(5-Cyanopyridin-3-ylethynyl)-2-fluoro-N,N-dimethylbenzamide

HRID 606898Notes

Reaction equation

HRID 606898 reaction equation
Cl.[CH3:2][NH:3][CH3:4].C(N(CC)C(C)C)(C)C.[C:14]([C:16]1[CH:17]=[C:18]([C:22]#[C:23][C:24]2[CH:25]=[CH:26][C:27]([F:33])=[C:28]([CH:32]=2)[C:29]([OH:31])=O)[CH:19]=[N:20][CH:21]=1)#[N:15].O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[C:14]([C:16]1[CH:17]=[C:18]([C:22]#[C:23][C:24]2[CH:25]=[CH:26][C:27]([F:33])=[C:28]([CH:32]=2)[C:29]([N:3]([CH3:4])[CH3:2])=[O:31])[CH:19]=[N:20][CH:21]=1)#[N:15]

Participants

7

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 670476775-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid

Product 1

HCID 670483405-(5-Cyanopyridin-3-ylethynyl)-2-fluoro-N,N-dimethylbenzamideYield 63.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add N-(3-dimethylaminopropyl)-N-ethylcarbodiamide hydrochloride (120 mg, 0.62 mmol) to a mixture of dimethylamine hydrochloride (51 mg, 0.62 mmol), N,N-diisopropylethylamine (108 μL, 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. Extract 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 30:70 to 50:50 with ethyl acetate:hexanes, to give the title compound as a white solid (104 mg, 63%).

Workup

  1. customan aqueous saturated solution of sodium bicarbonate and separate the layers
  2. extractionExtract the aqueous phase once with ethyl acetate
  3. extractionExtract 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 30:70 to 50:50 with ethyl acetate

Sources & evidence

ORD record
ord-dcad96ef49e84c3c9c8377f8c23d37a1
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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