3-Amino-4,4-difluorobut-2-enenitrile → HCID 67084928, compound

HRID 1484562Notes

Reaction equation

HRID 1484562 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1/[CH:11]=[C:12](/[C:14](=O)[CH3:15])\[CH3:13].[N:17]([O-])=O.[NH2:20][C:21]([CH:25]([F:27])[F:26])=[CH:22][C:23]#[N:24]>CC(O)C>[F:26][CH:25]([F:27])[C:21]1[NH:20][C:14]([CH3:15])=[C:12]([C:13]#[N:17])[CH:11]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[F:1])[NH:8][N:7]=[CH:6]3)[C:22]=1[C:23]#[N:24]

Participants

4

Reactant 2

HCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 131736731HCID 131736731, compound

Product 1

HCID 67084928HCID 67084928, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A suspension of 200 mg (0.87 mmol) (2E)-2-[(6-fluoro-1H-indazol-5-yl)methylidene]-3-oxobutane-nitrite (Example 6A) and 419 mg (3.49 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 31, 1 (1984)] in 2-propanol (1 ml) was stirred at reflux temperature overnight. After cooling, the mixture was concentrated under reduced pressure, and the residue was suspended in p-xylene (3 ml). Small amounts of p-toluenesulfonic acid and powdered 4 Å molecular sieve were added, and the mixture was stirred at reflux temperature for 16 h. Upon cooling, the mixture was diluted with aceto-nitrile and filtered. The filtrate was concentrated under reduced pressure, and the crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 9:1 v/v) to yield 81 mg (28% of th.) of the racemic title compound as a pale yellow solid.

Workup

  1. temperatureat reflux temperature overnight
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated under reduced pressure
  4. additionSmall amounts of p-toluenesulfonic acid and powdered 4 Å molecular sieve were added
  5. stirringthe mixture was stirred
  6. temperatureat reflux temperature for 16 h
  7. temperatureUpon cooling
  8. additionthe mixture was diluted with aceto-nitrile
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 9:1 v/v)

Sources & evidence

ORD record
ord-7d0d79fc37604bdf93cfe9e52ba1ebbd
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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