3-Amino-4,4-difluorobut-2-enenitrile → HCID 178437990, compound

HRID 1484567Notes

Reaction equation

HRID 1484567 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]=O)[CH:10]=2)[NH:5][N:4]=1)[CH3:2].[NH2:14][C:15]([CH:19]([F:21])[F:20])=[CH:16][C:17]#[N:18]>C(O)(=O)C.C1COCC1.CO>[F:20][CH:19]([F:21])[C:15]1[NH:14][C:15]([CH:19]([F:21])[F:20])=[C:16]([C:17]#[N:18])[CH:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[NH:5][N:4]=[C:3]3[CH2:1][CH3:2])[C:16]=1[C:17]#[N:18]

Participants

5

Reactant 2

HCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 178437999HCID 178437999, compound

Product 1

HCID 178437990HCID 178437990, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of 80 mg (0.46 mmol) 3-ethyl-1H-indazole-5-carbaldehyde (Example 10A), 119 mg (1.21 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)] and a trace amount of powdered 4 Å molecular sieve in acetic acid (0.44 ml) was heated to reflux temperature for 4 h. After cooling, the reaction mixture was diluted with THF/methanol and filtered. The filtrate was purified twice by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) yielding 99 mg (57% of th.) of the title compound.

Workup

  1. temperatureto reflux temperature for 4 h
  2. temperatureAfter cooling
  3. filtrationfiltered
  4. customThe filtrate was purified twice by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient)

Sources & evidence

ORD record
ord-b0293cf7f6e14dceba91813f2986e889
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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