Ammonium Acetate → HCID 178455690, compound

HRID 1484569Notes

Reaction equation

HRID 1484569 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8](/[CH:11]=[C:12](/[C:15](=O)[CH3:16])\[C:13]#[N:14])[CH:9]=2)[NH:4][N:3]=1.[F:18][C:19]([F:27])([CH2:25][CH3:26])[C:20](=O)[CH2:21][C:22]#[N:23].C([O-])(=O)C.[NH4+:32]>CC(O)C.C(O)(=O)C>[F:18][C:19]([C:20]1[NH:32][C:15]([CH3:16])=[C:12]([C:13]#[N:14])[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:21]=1[C:22]#[N:23])([F:27])[CH2:25][CH3:26]

Participants

6

Reactant 3

HCID 517165Ammonium AcetateHCID 86672503HCID 86672503, compoundHCID 178467936HCID 178467936, compound

Product 1

HCID 178455690HCID 178455690, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 113 mg (0.50 mmol) (2E)-2-[(3-methyl-1H-indazol-5-yl)methylidene]-3-oxobutanenitrile (Example 2A) and 432 mg (0.50 mmol based on 17% purity) 4,4-difluoro-3-oxohexanenitrile (Example 13A) in 2-propanol (334 μl) and acetic acid (170 μl) was treated with 116 mg (1.5 mmol) ammonium acetate and stirred for 20 min at 90° C. under microwave conditions. After cooling, the mixture was concentrated under reduced pressure, and the residue was suspended in p-xylene (1.5 ml). Small amounts of p-toluenesulfonic acid and powdered 4 Å molecular sieve were added, and the mixture was stirred at reflux temperature for 48 h. Upon cooling, the mixture was diluted with acetonitrile, filtered and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 9:1 v/v) followed by preparative thin layer silica gel chromatography (toluene/ethanol 5:1 v/v) to yield 7.2 mg (4% of th.) of the racemic title compound as a pale yellow solid.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated under reduced pressure
  3. additionSmall amounts of p-toluenesulfonic acid and powdered 4 Å molecular sieve were added
  4. stirringthe mixture was stirred
  5. temperatureat reflux temperature for 48 h
  6. temperatureUpon cooling
  7. additionthe mixture was diluted with acetonitrile
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 9:1 v/v)

Sources & evidence

ORD record
ord-d7e35deb18124f15b057e19d6a92bb37
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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