Cyanoacetic acid → 2-Cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acetamide

HRID 2406580Notes

Reaction equation

HRID 2406580 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C1C=NC2N(O)N=NC=2C=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH2:50]([N:52]([CH2:67][CH3:68])[CH2:53][CH2:54][O:55][C:56]1[CH:61]=[CH:60][C:59]([CH:62]([NH2:66])[CH2:63][CH2:64][CH3:65])=[CH:58][CH:57]=1)[CH3:51]>CN(C=O)C.C(OCC)(=O)C>[C:1]([CH2:3][C:4]([NH:66][CH:62]([C:59]1[CH:58]=[CH:57][C:56]([O:55][CH2:54][CH2:53][N:52]([CH2:67][CH3:68])[CH2:50][CH3:51])=[CH:61][CH:60]=1)[CH2:63][CH2:64][CH3:65])=[O:6])#[N:2]

Participants

8

Reactant 5

HCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66822143HCID 66822143, compound

Product 1

HCID 668220192-Cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acetamideYield 81.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cooled solution of cyanoacetic acid (37 mg, 0.43 mmol) in DMF (2 mL) was added 7-aza-1-hydroxybenzotriazole (HOAt; 59 mg, 0.43 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU; 165 mg, 0.43 mmol), diisopropylethylamine (DIPEA; 167 μL, 0.958 mmol) and 1-(4-(2-(diethylamino)ethoxy)phenyl)butan-1-amine (25; 115 mg, 0.43 mmol). The resulting mixture was then stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with sat. aqueous NaHCO3 (2×) and sat. brine, dried over sodium sulfate, and concentrated to a thick yellow oil. Purification by flash silica gel column chromatography, eluting with 5:95 methanol/dichloromethane, afforded 29 (116 mg, 80%) as a yellow oil: MS (ES+) m/z 332.2 (M+H)+.

Workup

  1. washwashed with sat. aqueous NaHCO3 (2×) and sat. brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated to a thick yellow oil
  4. customPurification by flash silica gel column chromatography
  5. washeluting with 5:95 methanol/dichloromethane

Sources & evidence

ORD record
ord-85628dcf14994fab9af901190173fd89
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

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