3-Amino-4,4-difluorobut-2-enenitrile → HCID 178434320, compound

HRID 1484560Notes

Reaction equation

HRID 1484560 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:11])=[N:7][NH:8]2)=[CH:4][C:3]=1[CH:12]=O.[NH2:14][C:15]([CH:19]([F:21])[F:20])=[CH:16][C:17]#[N:18]>C(O)(=O)C.C1COCC1>[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:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[F:1])[NH:8][N:7]=[C:6]3[CH3:11])[C:16]=1[C:17]#[N:18]

Participants

5

Reactant 2

HCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 178434325HCID 178434325, compound

Product 1

HCID 178434320HCID 178434320, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 100 mg (0.56 mmol) 6-fluoro-3-methyl-1H-indazole-5-carbaldehyde (Example 3A) and 146 mg (1.24 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 (0.54 ml) containing powdered 4 Å molecular sieve was heated to reflux temperature for 5 h. After cooling, the reaction mixture was diluted with THF and filtered. The filtrate was directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) yielding 136 mg (64% of th.) of the title compound.

Workup

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

Sources & evidence

ORD record
ord-5e2d9b5623954dcdac529de2d44343f1
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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