Acetic Acid → HCID 178434319, compound

HRID 1474451Notes

Reaction equation

HRID 1474451 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([C:6](/[C:8](=[CH:11]/[C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][C:20]=2[F:21])[NH:17][N:16]=[C:15]3[CH3:22])/[C:9]#[N:10])=O)=[CH:4][CH:3]=1.[NH2:25][C:26]([CH:30]([F:32])[F:31])=[CH:27][C:28]#[N:29].C(O)(=O)C>CC(O)C>[F:31][CH:30]([F:32])[C:26]1[NH:25][C:6]([C:5]2[CH:23]=[CH:24][C:2]([F:1])=[CH:3][CH:4]=2)=[C:8]([C:9]#[N:10])[CH:11]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][C:20]=2[F:21])[NH:17][N:16]=[C:15]3[CH3:22])[C:27]=1[C:28]#[N:29]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 178434324(2E)-3-(6-Fluoro-3-methyl-1H-indazol-5-yl)-2-[(4-fluorophenyl)carbonyl]prop-2-enenitrile

Product 1

HCID 178434319HCID 178434319, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 200 mg (0.569 mmol) (2E)-2-(4-fluorobenzoyl)-3-(6-fluoro-3-methyl-1H-indazol-5-yl)-prop-2-enenitrile (Example 5A) and 69 mg (0.569 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 for 12 h. Then, acetic acid (1.5 ml) was added, and stirring at reflux was continued for 6 h. Upon cooling, the mixture was concentrated under reduced pressure, and the residue was directly purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 80:20 v/v) to yield 36 mg (15% of th.) of the racemic title compound.

Workup

  1. temperatureat reflux for 12 h
  2. stirringstirring
  3. temperatureat reflux
  4. temperatureUpon cooling
  5. concentrationthe mixture was concentrated under reduced pressure
  6. customthe residue was directly purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 80:20 v/v)

Sources & evidence

ORD record
ord-6d7510aff16c45d29cccb66ca45200bd
Source dataset
uspto-grants-2015_04
Patent number
US09018234B2

Reaction notes

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