3-Amino-4,4-difluorobut-2-enenitrile → HCID 178434239, compound

HRID 1484559Notes

Reaction equation

HRID 1484559 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]=O)[CH:9]=2)[NH:4][N:3]=1.[NH2:13][C:14]([CH:18]([F:20])[F:19])=[CH:15][C:16]#[N:17]>C(O)(=O)C.CO.ClCCl>[F:19][CH:18]([F:20])[C:14]1[NH:13][C:14]([CH:18]([F:20])[F:19])=[C:15]([C:16]#[N:17])[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[CH3:1])[C:15]=1[C:16]#[N:17]

Participants

5

Reactant 2

HCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 178434286HCID 178434286, compound

Product 1

HCID 178434239HCID 178434239, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 80 mg (0.50 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A) and 130 mg (1.10 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 acetic acid (0.5 ml) containing powdered 4 Å molecular sieve was heated to reflux temperature for 3.5 h. After cooling, the reaction mixture was diluted with methanol/dichloromethane and filtered. The filtrate was evaporated, and the residue was purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) yielding 61 mg (34% of th.) of the title compound.

Workup

  1. temperaturewas heated
  2. temperatureto reflux temperature for 3.5 h
  3. temperatureAfter cooling
  4. filtrationfiltered
  5. customThe filtrate was evaporated
  6. customthe residue was purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient)

Sources & evidence

ORD record
ord-1749f805e3f745d69a8d924672a093eb
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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