6-fluoro-1H-indazole-5-carbaldehyde → HCID 68364207, compound

HRID 1484561Notes

Reaction equation

HRID 1484561 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]=O.[NH2:13][C:14]([CH:18]([F:20])[F:19])=[CH:15][C:16]#[N:17]>C(O)(=O)C.C1COCC1>[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:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[F:1])[NH:8][N:7]=[CH:6]3)[C:15]=1[C:16]#[N:17]

Participants

5

Reactant 2

HCID 579172916-fluoro-1H-indazole-5-carbaldehydeHCID 762236343-Amino-4,4-difluorobut-2-enenitrile

Product 1

HCID 68364207HCID 68364207, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 150 mg (0.55 mmol) 6-fluoro-1H-indazole-5-carbaldehyde (Example 5A) and 142 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)] in acetic acid (0.5 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 147 mg (72% 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-65e1cff75ec14df8aeba30f35ca2e2d9
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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