Dimethylformamide → N-(5-acetyl-2-fluorophenyl)cyclopropanecarboxamide

HRID 2189917Notes

Reaction equation

HRID 2189917 reaction equation
ClC1C(NC2C=C(C3CC3)NN=2)=NC(N[C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)C)=C(C=1)C#N.[CH:29]1([C:32]([OH:34])=O)[CH2:31][CH2:30]1.[CH3:35]CN(C(C)C)C(C)C.CN([CH:47]=[O:48])C>>[C:47]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([NH:14][C:32]([CH:29]2[CH2:31][CH2:30]2)=[O:34])[CH:11]=1)(=[O:48])[CH3:35]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 11711016(S)-5-Chloro-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2-(1-(5-fluoropyridin-2-yl)ethylamino)nicotinonitrile

Product 1

HCID 67427528N-(5-acetyl-2-fluorophenyl)cyclopropanecarboxamideYield 32%

Procedure

To a round, bottom flask was added 3-amino-4-fluoroacetophenone (Method 64, 1 g, 6.54 mmol), cyclopropyl carboxylic acid (0.62 ml, 7.84 mmol), HATu (2.5 g (6.57 mmol), and DIEA (2.3 ml, 13.08 mmol) in DMF (15 ml). The reaction mixture was allowed to stir at room temperature for 16 hours. The reaction mixture was quenched with water and partitioned with EtOAc. The layers were cut, followed by an additional wash of the aqueous with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue obtained was then purified by silica gel chromatography (Biotage Horizon System) using a gradient elution of 5-15% EtOAc in DCM to give 458 mg of the title compound (32% isolated yield). 1H NMR: 10.16 (s, 1H) 8.53 (dd, J=7.91, 2.26 Hz, 1H) 7.67-7.82 (m, 1H) 7.40 (dd, J=10.55, 8.67 Hz, 1H) 2.54 (s, 3H) 1.95-2.09 (m, 1H) 0.78-0.88 (m, 4H).

Workup

  1. customThe reaction mixture was quenched with water
  2. custompartitioned with EtOAc
  3. washan additional wash of the aqueous with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue obtained
  8. customwas then purified by silica gel chromatography (Biotage Horizon System)
  9. washa gradient elution of 5-15% EtOAc in DCM

Sources & evidence

ORD record
ord-9faafcd1533142dcb871bd2409b3cb7b
Source dataset
uspto-grants-2012_12
Patent number
US08324252B2

Reaction notes

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